CN106222281A - Test kit, application and method of based on the gene pleiomorphism accurate medication of guiding children patient - Google Patents
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Abstract
The invention discloses test kit, application and method of based on the gene pleiomorphism accurate medication of guiding children patient.Method is to select different gene detecting kits, and CYP1A2, CYP2B6, CYP2C8, CYP2C19, CYP2C9, CYP2D6, CYP2E1 are with CYP3A4 genetic polymorphism in detection.
Description
Technical field
The invention belongs to biological technical field, be specifically related to examination based on the gene pleiomorphism accurate medication of guiding children patient
Agent box, application and method.
Background technology
Drug safety is related to that national economy and social stability, World Health Organization's investigation are pointed out, whole world patient has three points
One of be to die from non-rational use of drug rather than disease itself.China's non-rational use of drug and drug dependence phenomenon are very serious, become
For restriction China national health, the key factor of social development.The patient that China is in hospital because of severe drug untoward reaction every year
Up to 2,500,000 people, annual lethal number is up to more than 50 ten thousand people；In more than 100 ten thousand deaf-mute childs, about 50% is drug-induced deafness, gives
Country causes huge medical expense burden and social economical burden.Owing to child is in continuous growth and development stage, different
The each system of age bracket body, organ function the most immature and perfect, to absorption, the metabolism of medicine, be distributed, drain difference very
Greatly, and the most different to the reaction of medicine in different year section sections.Therefore, child's medicine clinically unreasonable use phenomenon is more
Add sternness.National drug untoward reaction inspection center data show, child's adverse reaction rate is up to 12.9%.
Summary of the invention
The present invention refer to use Pharmacogenetics Knowledge or/and Drug Discovery is gained knowledge, according to CYP1A2, CYP2B6,
CYP2C8, CYP2C19, CYP2C9, CYP2D6, CYP2E1 rationally use with CYP3A4 genetic polymorphism guiding children patient safety
Medicine.Specifically include herein below:
Following gene pleiomorphism can be used for preparing guiding children patient accurate medication test kit:
(1) CYP1A2: comprise rs11636419, rs12720461, rs2069514, rs2069522, rs2069526,
rs2470890、rs2472299、rs2472300、rs2472304、rs28399424、rs35694136、rs3743484、
rs45564134、rs4646425、rs4646427、rs55889066、rs56276455、rs762551、rs72547516、
One or more combinations in rs72547517, rs72547513, rs72547511, rs72547515 polymorphism or haplotype；
(2) CYP2B6: comprise rs10403955, rs1042389, rs12721646, rs12721655, rs139801276,
rs186335453、rs2054675、rs2279343、rs2279344、rs2279345、rs281864907、rs28399499、
rs3211371、rs34097093、rs34223104、rs35303484、rs35979566、rs36118214、rs36079186、
rs371424910、rs373489637、rs3745274、rs3786547、rs45482602、rs4802101、rs4802104、
rs4803419、rs58425034、rs707265、rs7254579、rs7260329、rs8109848、rs8192709、
One or more combinations in rs8192719 polymorphism or the gene of haplotype；
(3) CYP2C8: comprise rs10509681, rs1058930, rs1058932, rs1113129, rs11572076,
rs11572080、rs11572103、rs11572177、rs1341162、rs1341164、rs17110453、rs193451、
rs1934951、rs1934953、rs1934980、rs2071426、rs2275622、rs3832694、rs66501115、
One or more combinations in rs7909236 polymorphism or haplotype；
(4) CYP2C19: comprise rs11188072, rs12248560, rs12767583, rs12768009,
rs12769205、rs12773342、rs145119820、rs17878459、rs17879685、rs17882687、
rs17884712、rs28399504、rs3758581、rs3814637、rs41291556、rs4244285、rs4917623、
rs4986893、rs4986894、rs55640102、rs55752064、rs55948420、rs56337013、rs57081121、
rs5787121、rs58973490、rs6413438、rs6583954、rs72552267、rs72558184、rs72558185、
One or more combinations in rs72558186 polymorphism or haplotype；
(5) CYP2C9: comprise rs10509680, rs1057909, rs1057910, rs1057911, rs12572351,
rs12782374、rs141011391、rs17847042、rs1799853、rs1934963、rs1934967、rs1934968、
rs1934969、rs2017319、rs2256871、rs28371685、rs28371686、rs2860905、rs4086116、
rs4917639、rs4918758、rs56165452、rs67807361、rs7089580、rs71486745、rs72558187、
rs72558188、rs72558189、rs72558190、rs72558191、rs7900194、rs9332094、rs9332096、
rs9332104、rs9332120、rs9332127、rs9332130、rs9332131、rs9332146、rs9332174、
One or more combinations in rs9332197, rs9332238, rs9332239 polymorphism or haplotype；
(6) CYP2D6: comprise rs1065852, rs1080983, rs1080985, rs1080989, rs1135840,
rs1135824、rs138417770、rs16947、rs28360521、rs28371706、rs28371725、rs28371733、
rs35742686、rs367543000、rs371793722、rs3892097、rs5030655、rs5030656、rs5030862、
rs5030863、rs5030865、rs5030867、rs567606867、rs59421388、rs61736512、rs72549354、
One or more in rs745746329, rs74966855, rs750996195, rs76088846, rs777560972 polymorphism
Combination or haplotype；
(7) CYP2E1: comprise rs1329149, rs2031920, rs2070672, rs2070673, rs2070676,
rs2249694、rs2249695、rs2480256、rs2515641、rs2515644、rs3813865、rs3813867、
rs4646976、rs55897648、rs6413419、rs6413420、rs6413432、rs72559710、rs743535、
In rs8192772, rs8192775, rs8192766, rs8192780, rs915906, rs915908, rs915909 polymorphism
One or more combinations or haplotype；
(8) CYP3A4: comprise rs1041988, rs12333983, rs12721627, rs12721629, rs12721634,
rs1851426、rs2242480、rs2246709、rs2687116、rs2740574、rs28371759、rs3091339、
rs3208361、rs3208363、rs35599367、rs3735451、rs45614732、rs4646437、rs4646438、
rs4646440、rs4986907、rs4986908、rs4986909、rs4986910、rs4986913、rs4986914、
rs4987161、rs55785340、rs55901263、rs55951658、rs56324128、rs67666821、rs67784355、
One or more combinations in rs6956344, rs72552799 polymorphism or haplotype.
In preparing guiding children patient accurate medication test kit, detection said gene is contained polymorphic based on gene pleiomorphism
The primer of property.
It is to select different gene test examination based on gene pleiomorphism in the method preparing the accurate medication of guiding children patient
Agent box, CYP1A2, CYP2B6, CYP2C8, CYP2C19, CYP2C9, CYP2D6, CYP2E1 are with CYP3A4 genetic polymorphism in detection.
Specifically, described CYP1A2, CYP2B6, CYP2C8, CYP2C19, CYP2C9, CYP2D6, CYP2E1 are many with CYP3A4 heredity
State property refers to above-mentioned 8 gene pleiomorphism.
The invention will be further described below:
Cytochrome P 450 enzymes in liver plays an important role in drug metabolism processes.Topmost metabolic enzyme in human body
There are CYP1A2, CYP2B6, CYP2C8, CYP2C19, CYP2C9, CYP2D6, CYP2E1 with CYP3A4.The activity of these metabolic enzymes
Change influences whether the metabolism of medicine, and then has influence on curative effect of medication or/and toxic reaction.Research shows that genetic polymorphism is shadow
Ring the main cause of these metabolic enzyme activities, instruct the clinical practice of medicine according to genetic polymorphism, can significantly reduce bad
Reaction risk.Existing research is carried out mostly in adult, it has been found that child patient clinic is used by P450 enzyme genetic polymorphism
The reasons such as the directive significance of medicine is bigger, and this may be accustomed to relatively merely to children life, merging disease is few are relevant.Therefore, this
Bright it is mainly based upon Pharmacogenetics Knowledge or/and Drug Discovery is gained knowledge, according to metabolic enzyme genetic polymorphism guiding children
Patient clinical safe and reasonable medication, particular content is as follows:
CYP1A2: 1. CYP1A2 genetic polymorphism (rs11636419, rs12720461, rs2069514, rs2069522,
rs2069526、rs2470890、rs2472299、rs2472300、rs2472304、rs28399424、rs35694136、
rs3743484、rs45564134、rs4646425、rs4646427、rs55889066、rs56276455、rs762551、
Rs72547516, rs72547517, rs72547513, rs72547511, rs72547515) in any one polymorphism, all
Can the reasonable application in clinical child patient of medicine in guidance table 1, if occur simultaneously, the polymorphism of 2 or more than 2 refers to
Lead effect higher.2. CYP1A2 genetic polymorphism (rs11636419, rs12720461, rs2069514, rs2069522,
rs2069526、rs2470890、rs2472299、rs2472300、rs2472304、rs28399424、rs35694136、
rs3743484、rs45564134、rs4646425、rs4646427、rs55889066、rs56276455、rs762551、
Rs72547516, rs72547517, rs72547513, rs72547511, rs72547515) in one or more polymorphism groups
The haplotype become, it is possible to the reasonable application in clinical child patient of the medicine in guidance table 1.3. ciprofloxacin
(Ciprofloxacin), nafcillin (Nafcilline), cimetidine (Cimetidine), Mibefradil
(Mibefradil), amiodarone (Amiodarone), Mibefradil (Mibefradil), fluvoxamine (Fluvoxamine), first
The medicines such as oxygen sarin (Methoxsalen), the furan film (Furafylline) can suppress the activity of CYP1A2 enzyme, these medicines
During with Drug combination in table 1, the metabolism of medicine in table 1 can be reduced, so affect medicine in table 1 curative effect or/
And toxic reaction.4. albendazole (Albendazole), lansoprazole (Lansoprazole), primaquine (Primaquine),
The medicines such as omeprazole (Omeprazole), modafinil (Modafinil) can induce the activity of CYP1A2 enzyme, these medicines with
During Drug combination in table 1, can the metabolism of medicine in accelerometer 1, and then affect medicine in table 1 curative effect or/and
Toxic reaction.
Table 1
CYP2B6: 1. CYP2B6 genetic polymorphism (rs10403955, rs1042389, rs12721646, rs12721655,
rs139801276、rs186335453、rs2054675、rs2279343、rs2279344、rs2279345、rs281864907、
rs28399499、rs3211371、rs34097093、rs34223104、rs35303484、rs35979566、rs36118214、
rs36079186、rs371424910、rs373489637、rs3745274、rs3786547、rs45482602、rs4802101、
rs4802104、rs4803419、rs58425034、rs707265、rs7254579、rs7260329、rs8109848、
Rs8192709, rs8192719) in any one polymorphism, all can medicine in guidance table 2 in clinical child patient
Rationally application, if occur simultaneously, the polymorphism directive function of 2 or more than 2 is higher.2. CYP2B6 genetic polymorphism
(rs10403955、rs1042389、rs12721646、rs12721655、rs139801276、rs186335453、
rs2054675、rs2279343、rs2279344、rs2279345、rs281864907、rs28399499、rs3211371、
rs34097093、rs34223104、rs35303484、rs35979566、rs36118214、rs36079186、
rs371424910、rs373489637、rs3745274、rs3786547、rs45482602、rs4802101、rs4802104、
rs4803419、rs58425034、rs707265、rs7254579、rs7260329、rs8109848、rs8192709、
The haplotype of the one or more polymorphisms composition in rs8192719), it is possible to the medicine in guidance table 1 is at clinical child patient
In reasonable application.3. clopidogrel (Clopidogrel), ethinylestradiol (Ethinyl estradiol), tespamin
(Thiotepa), the medicine such as ticlopidine (Ticlopidine) can suppress the activity of CYP2B6 enzyme, these medicines with in table 1
During Drug combination, the metabolism of medicine in table 2 can be reduced, and then affect the curative effect of medicine in table 2 or/and toxicity is anti-
Should.4. carbamazepine (Carbamazepine), cyclophosphamide (Cyclophosphamide), Sustiva (Efavirenz),
Nevirapine (Nevirapine), phenobarbital (Phenobarbital), phenytoin (Phenytoin), rifampicin
Etc. (Rifampin) medicine can induce the activity of CYP2B6 enzyme, when these medicines and Drug combination in table 2, and can accelerometer
The metabolism of the medicine in 2, and then affect the curative effect of medicine in table 2 or/and toxic reaction.
Table 2
CYP2C8: 1. CYP2C8 gene pleiomorphism (rs10509681, rs1058930, rs1058932, rs1113129,
rs11572076、rs11572080、rs11572103、rs11572177、rs1341162、rs1341164、rs17110453、
rs193451、rs1934951、rs1934953、rs1934980、rs2071426、rs2275622、rs3832694、
Rs66501115, rs7909236) in any one polymorphism, all can medicine in guidance table 3 in clinical child patient
Rationally application, if occur simultaneously, the polymorphism directive function of 2 or more than 2 is higher.2. CYP2C8 gene pleiomorphism
(rs10509681、rs1058930、rs1058932、rs1113129、rs11572076、rs11572080、rs11572103、
rs11572177、rs1341162、rs1341164、rs17110453、rs193451、rs1934951、rs1934953、
Rs1934980, rs2071426, rs2275622, rs3832694, rs66501115, rs7909236) in one or more many
The haplotype of state property composition, it is possible to the reasonable application in clinical child patient of the medicine in guidance table 3.3. gemfibrozil
(gemfibrozil), trimethoprim (trimethoprim), glitazone (glitazones), montelukast
(montelukast), the medicine such as Quercetin (quercetin) can suppress the activity of CYP2C8 enzyme, these medicines and the medicine in table 3
During thing use in conjunction, the metabolism of medicine in table 3 can be reduced, and then affect the curative effect of medicine in table 3 or/and toxic reaction.
4. the medicine such as rifampicin (Rifampin) can induce the activity of CYP2C8 enzyme, when these medicines and Drug combination in table 3,
Can the metabolism of medicine in accelerometer 3, and then affect the curative effect of medicine in table 3 or/and toxic reaction.
Table 3
CYP2C19: 1. CYP2C19 gene pleiomorphism (rs11188072, rs12248560, rs12767583,
rs12768009、rs12769205、rs12773342、rs145119820、rs17878459、rs17879685、
rs17882687、rs17884712、rs28399504、rs3758581、rs3814637、rs41291556、rs4244285、
rs4917623、rs4986893、rs4986894、rs55640102、rs55752064、rs55948420、rs56337013、
rs57081121、rs5787121、rs58973490、rs6413438、rs6583954、rs72552267、rs72558184、
Rs72558185, rs72558186) in any one polymorphism, all can medicine in guidance table 4 in clinical child patient
Reasonable application, if occur simultaneously, the polymorphism directive function of 2 or more than 2 is higher.2. CYP2C19 gene pleiomorphism
(rs11188072、rs12248560、rs12767583、rs12768009、rs12769205、rs12773342、
rs145119820、rs17878459、rs17879685、rs17882687、rs17884712、rs28399504、rs3758581、
rs3814637、rs41291556、rs4244285、rs4917623、rs4986893、rs4986894、rs55640102、
rs55752064、rs55948420、rs56337013、rs57081121、rs5787121、rs58973490、rs6413438、
Rs6583954, rs72552267, rs72558184, rs72558185, rs72558186) in one or more polymorphism groups
The haplotype become, it is possible to the reasonable application in clinical child patient of the medicine in guidance table 4.3. chloromycetin
(chloramphenicol), cimetidine (cimetidine), felbamate (felbamate), fluoxetine
(fluoxetine), fluvoxamine (fluvoxamine), indomethacin (indomethacin), ketoconazole
(ketoconazole), lansoprazole (lansoprazole), modafinil (modafinil), omeprazole
(omeprazole), oxcarbazepine (oxcarbazepine), probenecid (probenecid), ticlopidine
(ticlopidine), topiramate (topiramate), pantoprazole (pantoprazole), rabeprazole (rabeprazole)
The activity of CYP2C19 enzyme can be suppressed Deng medicine, during Drug combination in these medicines and table 4, the medicine in table 4 can be reduced
Metabolism, and then affect the curative effect of medicine in table 4 or/and toxic reaction.4. carbamazepine (carbamazepine), alkynes promise
Ketone (norethindrone), prednisone (prednisone), rifampicin (rifampin), pentobarbital (pentobarbital)
The activity of CYP2C19 enzyme can be induced Deng medicine, during Drug combination in these medicines and table 4, can medicine in accelerometer 4
Metabolism, and then affect the curative effect of medicine in table 4 or/and toxic reaction.
Table 4
CYP2C9: 1. CYP2C9 gene pleiomorphism (rs10509680, rs1057909, rs1057910, rs1057911,
rs12572351、rs12782374、rs141011391、rs17847042、rs1799853、rs1934963、rs1934967、
rs1934968、rs1934969、rs2017319、rs2256871、rs28371685、rs28371686、rs2860905、
rs4086116、rs4917639、rs4918758、rs56165452、rs67807361、rs7089580、rs71486745、
rs72558187、rs72558188、rs72558189、rs72558190、rs72558191、rs7900194、rs9332094、
rs9332096、rs9332104、rs9332120、rs9332127、rs9332130、rs9332131、rs9332146、
Rs9332174, rs9332197, rs9332238, rs9332239) in any one polymorphism, all can medicine in guidance table 5
The thing reasonable application in clinical child patient, if occur simultaneously, the polymorphism directive function of 2 or more than 2 is higher.②
CYP2C9 gene pleiomorphism (rs10509680, rs1057909, rs1057910, rs1057911, rs12572351,
rs12782374、rs141011391、rs17847042、rs1799853、rs1934963、rs1934967、rs1934968、
rs1934969、rs2017319、rs2256871、rs28371685、rs28371686、rs2860905、rs4086116、
rs4917639、rs4918758、rs56165452、rs67807361、rs7089580、rs71486745、rs72558187、
rs72558188、rs72558189、rs72558190、rs72558191、rs7900194、rs9332094、rs9332096、
rs9332104、rs9332120、rs9332127、rs9332130、rs9332131、rs9332146、rs9332174、
Rs9332197, rs9332238, rs9332239) in one or more polymorphisms composition haplotype, it is possible in guidance table 5
The medicine reasonable application in clinical child patient.3. amiodarone (Amiodarone), fluconazol (Fluconazole), non-
Nobert (Fenofibrate), fluvastatin (Fluvastatin), fluvoxamine (fluvoxamine), isoniazid
(isoniazid), lovastatin (lovastatin), paroxetine (paroxetine), Phenylbutazone/bute
(phenylbutazone), probenecid (probenicid), Sertraline (sertraline), sulfamethoxazole
(sulfamethoxazole), sulfaphenazole (sulfaphenazole), teniposide (teniposide), voriconazole
(voriconazole), the medicine such as trimethoprim (trimethoprim), zafirlukast (zafirlukast) can suppress
The activity of CYP2C9 enzyme, during Drug combination in these medicines and table 5, can reduce the metabolism of medicine in table 5, Jin Erying
Ring the curative effect of medicine in table 5 or/and toxic reaction.4. rifampicin (rifampin), quinalbarbitone (secobarbital)
The activity of CYP2C9 enzyme can be induced Deng medicine, during Drug combination in these medicines and table 5, can medicine in accelerometer 5
Metabolism, and then affect the curative effect of medicine in table 5 or/and toxic reaction.
Table 5
CYP2D6: 1. CYP2D6 gene pleiomorphism (rs1065852, rs1080983, rs1080985, rs1080989,
rs1135840、rs1135824、rs138417770、rs16947、rs28360521、rs28371706、rs28371725、
rs28371733、rs35742686、rs367543000、rs371793722、rs3892097、rs5030655、rs5030656、
rs5030862、rs5030863、rs5030865、rs5030867、rs567606867、rs59421388、rs61736512、
Rs72549354, rs745746329, rs74966855, rs750996195, rs76088846, rs777560972) in any
One polymorphism, all can the reasonable application in clinical child patient of medicine in guidance table 6, if occur simultaneously 2 or 2 with
On polymorphism directive function higher.2. CYP2D6 gene pleiomorphism (rs1065852, rs1080983, rs1080985,
rs1080989、rs1135840、rs1135824、rs138417770、rs16947、rs28360521、rs28371706、
rs28371725、rs28371733、rs35742686、rs367543000、rs371793722、rs3892097、rs5030655、
rs5030656、rs5030862、rs5030863、rs5030865、rs5030867、rs567606867、rs59421388、
rs61736512、rs72549354、rs745746329、rs74966855、rs750996195、rs76088846、
The haplotype of the one or more polymorphisms composition in rs777560972), it is possible to the medicine in guidance table 6 is suffered from clinical child
Reasonable application in person.3. amiodarone (amiodarone), BUP (buproprion), celecoxib
(celecoxib), chlorphenamine (chlorpheniramine), chlorpromazine (chlorpromazine), cimetidine/cimetidine
(cimetidine), Sertraline (sertraline), citalopram (citalopram), clemastine (clemastine), chlorine
Imipramine/clomipramine (clomipramine), ***e (***e), diphenhydramine (diphenhydramine), worry too much
Flat (doxepin), amycin/doxorubicin (doxorubicin), escitalopram/escitalopram (escitalopram),
Fluoxetine (fluoxetine), Halofantrine (halofantrine), methotrimeprazine (levomepromazine), metoclopramide
(metoclopramide), methadone (methadone), mibefradil (mibefradil), midodrine
(midodrine), moclobemide (moclobemide), paroxetine (paroxetine), quinidine (quinidine), degree Lip river
Xi Ting (duloxetine), terbinafine (terbinafine), perphenazine (perphenazine), atarax
(hydroxyzine), ranitidine (ranitidine), haloperidol (haloperidol), ritonavir (ritonavir),
The medicines such as ticlopidine (ticlopidine), tripelennamine (tripelennamine) can suppress the activity of CYP2D6 enzyme, these
During Drug combination in medicine and table 6, the metabolism of medicine in table 6 can be reduced, and then affect the curative effect of medicine in table 6
Or/and toxic reaction.4. the medicine such as dexamethasone (dexamethasone), rifampicin (rifampin) can induce CYP2D6 enzyme
Activity, during Drug combination in these medicines and table 6, can the metabolism of medicine in accelerometer 6, and then affect in table 6
The curative effect of medicine or/and toxic reaction.
Table 6
CYP2E1: 1. CYP2E1 gene pleiomorphism (rs1329149, rs2031920, rs2070672, rs2070673,
rs2070676、rs2249694、rs2249695、rs2480256、rs2515641、rs2515644、rs3813865、
rs3813867、rs4646976、rs55897648、rs6413419、rs6413420、rs6413432、rs72559710、
rs743535、rs8192772、rs8192775、rs8192766、rs8192780、rs915906、rs915908、rs915909)
In any one polymorphism, all can the reasonable application in clinical child patient of medicine in guidance table 7, if occur 2 simultaneously
Individual or more than 2 polymorphism directive function is higher.2. CYP2E1 gene pleiomorphism (rs1329149, rs2031920,
rs2070672、rs2070673、rs2070676、rs2249694、rs2249695、rs2480256、rs2515641、
rs2515644、rs3813865、rs3813867、rs4646976、rs55897648、rs6413419、rs6413420、
rs6413432、rs72559710、rs743535、rs8192772、rs8192775、rs8192766、rs8192780、
Rs915906, rs915908, rs915909) in one or more polymorphisms composition haplotype, it is possible to the medicine in guidance table 7
The thing reasonable application in clinical child patient.3. the medicine such as ethanol (ethanol), isoniazid (isoniazid) can be induced
The activity of CYP2E1 enzyme, during Drug combination in these medicines and table 7, can the metabolism of medicine in accelerometer 7, Jin Erying
Ring the curative effect of medicine in table 7 or/and toxic reaction.
Table 7
CYP3A4: 1. CYP3A4 gene pleiomorphism (rs1041988, rs12333983, rs12721627, rs12721629,
rs12721634、rs1851426、rs2242480、rs2246709、rs2687116、rs2740574、rs28371759、
rs3091339、rs3208361、rs3208363、rs35599367、rs3735451、rs45614732、rs4646437、
rs4646438、rs4646440、rs4986907、rs4986908、rs4986909、rs4986910、rs4986913、
rs4986914、rs4987161、rs55785340、rs55901263、rs55951658、rs56324128、rs67666821、
Rs67784355, rs6956344, rs72552799) in any one polymorphism, all can medicine in guidance table 8 in clinic
Reasonable application in child patient, if occur simultaneously, the polymorphism directive function of 2 or more than 2 is higher.2. CYP3A4 gene
Polymorphism (rs1041988, rs12333983, rs12721627, rs12721629, rs12721634, rs1851426,
rs2242480、rs2246709、rs2687116、rs2740574、rs28371759、rs3091339、rs3208361、
rs3208363、rs35599367、rs3735451、rs45614732、rs4646437、rs4646438、rs4646440、
rs4986907、rs4986908、rs4986909、rs4986910、rs4986913、rs4986914、rs4987161、
rs55785340、rs55901263、rs55951658、rs56324128、rs67666821、rs67784355、rs6956344、
The haplotype of the one or more polymorphisms composition in rs72552799), it is possible to the medicine in guidance table 8 is at clinical child patient
In reasonable application.3. indinavir (indinavir), viracept see nelfinaivr (nelfinavir), ritonavir (ritonavir),
Saquinavir (saquinavir), Ketek (Telithromycin), Aprepitant (aprepitant), amiodarone
(amiodarone), azithromycin (azithromycin), chloromycetin (chloramphenicol), cimetidine
(cimetidine), ciprofloxacin (ciprofloxacin), clarithromycin (clarithromycin), diltiazem
(diltiazem), erythromycin (erythromycin), fluconazol (fluconazole), fluvoxamine (fluvoxamine), pregnant
Dienone (gestodene), grapefruit juice (grapefruit juice), itraconazole (itraconazole), ketoconazole
(ketoconazole), mifepristone (mifepristone), nefazodone (nefazodone), norfloxacin
(norfloxacin), norfluoxetine (norfluoxetine), mibefradil (mibefradil), verapamil
(verapamil), the medicine such as imatinib (imatinib), voriconazole (voriconazole) can suppress the work of CYP3A4 enzyme
Property, during Drug combination in these medicines and table 8, the metabolism of medicine in table 8 can be reduced, and then affect the medicine in table 8
The curative effect of thing is or/and toxic reaction.4. efavirenz (efavirenz), nevirapine (nevirapine), barbiturate
(barbiturates), carbamazepine (carbamazepine), glucocorticoid (glucocorticoids), modafinil
(modafinil), oxcarbazepine (oxcarbazepine), phenobarbital rice that (phenobarbital), phenytoin
(phenytoin), rifampicin (rifampin), Herba Hyperici perforati (St.John's wort), troglitazone (troglitazone),
The medicines such as pioglitazone (pioglitazone), rifabutin (rifabuti) can induce the activity of CYP3A4 enzyme, these medicines
During with Drug combination in table 8, can the metabolism of medicine in accelerometer 8, and then affect medicine in table 8 curative effect or/
And toxic reaction.
Table 8
Detailed description of the invention
1. gather peripheral vein blood sample or mouth desquamated cells.
2. extract genomic DNA.
3. select different gene detecting kit, detection CYP1A2, CYP2B6, CYP2C8, CYP2C19, CYP2C9,
CYP2D6, CYP2E1 are with CYP3A4 genetic polymorphism:
(1) CYP1A2: comprise rs11636419, rs12720461, rs2069514, rs2069522, rs2069526,
rs2470890、rs2472299、rs2472300、rs2472304、rs28399424、rs35694136、rs3743484、
rs45564134、rs4646425、rs4646427、rs55889066、rs56276455、rs762551、rs72547516、
One or more combinations in rs72547517, rs72547513, rs72547511, rs72547515 polymorphism or haplotype
Gene detecting kit.
(2) CYP2B6: comprise rs10403955, rs1042389, rs12721646, rs12721655, rs139801276,
rs186335453、rs2054675、rs2279343、rs2279344、rs2279345、rs281864907、rs28399499、
rs3211371、rs34097093、rs34223104、rs35303484、rs35979566、rs36118214、rs36079186、
rs371424910、rs373489637、rs3745274、rs3786547、rs45482602、rs4802101、rs4802104、
rs4803419、rs58425034、rs707265、rs7254579、rs7260329、rs8109848、rs8192709、
One or more combinations in rs8192719 polymorphism or the gene detecting kit of haplotype.
(3) CYP2C8: comprise rs10509681, rs1058930, rs1058932, rs1113129, rs11572076,
rs11572080、rs11572103、rs11572177、rs1341162、rs1341164、rs17110453、rs193451、
rs1934951、rs1934953、rs1934980、rs2071426、rs2275622、rs3832694、rs66501115、
One or more combinations in rs7909236 polymorphism or the gene detecting kit of haplotype.
(4) CYP2C19: comprise rs11188072, rs12248560, rs12767583, rs12768009,
rs12769205、rs12773342、rs145119820、rs17878459、rs17879685、rs17882687、
rs17884712、rs28399504、rs3758581、rs3814637、rs41291556、rs4244285、rs4917623、
rs4986893、rs4986894、rs55640102、rs55752064、rs55948420、rs56337013、rs57081121、
rs5787121、rs58973490、rs6413438、rs6583954、rs72552267、rs72558184、rs72558185、
One or more combinations in rs72558186 polymorphism or the gene detecting kit of haplotype.
(5) CYP2C9: comprise rs10509680, rs1057909, rs1057910, rs1057911, rs12572351,
rs12782374、rs141011391、rs17847042、rs1799853、rs1934963、rs1934967、rs1934968、
rs1934969、rs2017319、rs2256871、rs28371685、rs28371686、rs2860905、rs4086116、
rs4917639、rs4918758、rs56165452、rs67807361、rs7089580、rs71486745、rs72558187、
rs72558188、rs72558189、rs72558190、rs72558191、rs7900194、rs9332094、rs9332096、
rs9332104、rs9332120、rs9332127、rs9332130、rs9332131、rs9332146、rs9332174、
One or more combinations in rs9332197, rs9332238, rs9332239 polymorphism or the gene detection reagent of haplotype
Box.
(6) CYP2D6: comprise rs1065852, rs1080983, rs1080985, rs1080989, rs1135840,
rs1135824、rs138417770、rs16947、rs28360521、rs28371706、rs28371725、rs28371733、
rs35742686、rs367543000、rs371793722、rs3892097、rs5030655、rs5030656、rs5030862、
rs5030863、rs5030865、rs5030867、rs567606867、rs59421388、rs61736512、rs72549354、
One or more in rs745746329, rs74966855, rs750996195, rs76088846, rs777560972 polymorphism
Combination or the gene detecting kit of haplotype.
(7) CYP2E1: comprise rs1329149, rs2031920, rs2070672, rs2070673, rs2070676,
rs2249694、rs2249695、rs2480256、rs2515641、rs2515644、rs3813865、rs3813867、
rs4646976、rs55897648、rs6413419、rs6413420、rs6413432、rs72559710、rs743535、
In rs8192772, rs8192775, rs8192766, rs8192780, rs915906, rs915908, rs915909 polymorphism
One or more combinations or the gene detecting kit of haplotype.
(8) CYP3A4: comprise rs1041988, rs12333983, rs12721627, rs12721629, rs12721634,
rs1851426、rs2242480、rs2246709、rs2687116、rs2740574、rs28371759、rs3091339、
rs3208361、rs3208363、rs35599367、rs3735451、rs45614732、rs4646437、rs4646438、
rs4646440、rs4986907、rs4986908、rs4986909、rs4986910、rs4986913、rs4986914、
rs4987161、rs55785340、rs55901263、rs55951658、rs56324128、rs67666821、rs67784355、
One or more combinations in rs6956344, rs72552799 polymorphism or the gene detecting kit of haplotype.
4. use the result of gene detecting kit according to detection, instruct clinical child patient rational use of drug.
(1) CYP1A2: if child patient occur rs11636419, rs12720461, rs2069514, rs2069522,
rs2069526、rs2470890、rs2472299、rs2472300、rs2472304、rs28399424、rs35694136、
rs3743484、rs45564134、rs4646425、rs4646427、rs55889066、rs56276455、rs72547516、
In rs72547517, rs72547513, rs72547511, rs72547515 polymorphism one, child patient uses in table 1
During medicine, it is contemplated that reduce using dosage；If occurring, the combination of multiple polymorphism or haplotype are positive, and child patient uses in table 1
Medicine time, it should be noted that monitoring, it is possible to decrease using dosage or change dressings.If there is rs762551 polymorphism, child patient uses table 1
In medicine time, it is contemplated that increase using dosage.If said gene polymorphism is feminine gender, child patient uses the medicine in table 1
Thing can use routinely in medicine explanation.But when the medicine in table 1, (ciprofloxacin, nafcillin, western miaow replace with CYP1A2 inhibitor
Fourth, Mibefradil, amiodarone, Mibefradil, fluvoxamine, methoxsalen, the furan film etc.) when being used in combination, should suitably subtract
Few using dosage, especially in CYP1A2 gene pleiomorphism (not comprising rs762551) child patient.But when the medicine in table 1
When being used in combination with CYP1A2 derivant (albendazole, lansoprazole, primaquine, omeprazole, modafinil etc.), CYP1A1
Wild type patient can suitably increase using dosage, but sudden change (not comprising rs762551) patient it is contemplated that according to conventional description to
Medicine.
(2) CYP2B6: if child patient occur rs10403955, rs1042389, rs12721646, rs12721655,
rs139801276、rs186335453、rs2054675、rs2279343、rs2279344、rs2279345、rs281864907、
rs28399499、rs3211371、rs34097093、rs34223104、rs35303484、rs35979566、rs36118214、
rs36079186、rs371424910、rs373489637、rs3745274、rs3786547、rs45482602、rs4802101、
rs4802104、rs4803419、rs58425034、rs707265、rs7254579、rs7260329、rs8109848、
In rs8192709, rs8192719 polymorphism one, when child patient uses the medicine in table 2, it is contemplated that reduces and uses agent
Amount；If occurring, the combination of multiple polymorphism or haplotype are positive, when child patient uses the medicine in table 2, it should be noted that monitoring, can drop
Low using dosage or change dressings.If said gene polymorphism is feminine gender, child patient uses the medicine in table 2 can medicine routinely
Illustrate to use.But when the medicine in table 2 joins with CYP2B6 inhibitor (clopidogrel, ethinylestradiol, tespamin, ticlopidine etc.)
When closing use, should suitably reduce using dosage, especially in CYP2B6 gene pleiomorphism child patient.But when the medicine in table 2
Thing and CYP2B6 derivant (carbamazepine, cyclophosphamide, Sustiva, nevirapine, phenobarbital, phenytoin, rifampicin
Deng) be used in combination time, CYP2B6 wild type patient can suitably increase using dosage, but sudden change patient is it is contemplated that illustrate according to routine
Book is administered.
(3) CYP2C8: if child patient occur rs10509681, rs1058930, rs1058932, rs1113129,
rs11572076、rs11572080、rs11572103、rs11572177、rs1341162、rs1341164、rs17110453、
rs193451、rs1934951、rs1934953、rs1934980、rs2071426、rs2275622、rs3832694、
In rs66501115, rs7909236 polymorphism one, when child patient uses the medicine in table 3, it is contemplated that reduces and uses agent
Amount；If occurring, the combination of multiple polymorphism or haplotype are positive, when child patient uses the medicine in table 3, it should be noted that monitoring, can drop
Low using dosage or change dressings.If said gene polymorphism is feminine gender, child patient uses the medicine in table 3 can medicine routinely
Illustrate to use.But when the medicine in table 3 and CYP2C8 inhibitor (gemfibrozil, trimethoprim, glitazone, Meng
Lu Site, Quercetin etc.) when being used in combination, should suitably reduce using dosage, especially suffer from CYP2C8 gene pleiomorphism child
In person.But when the medicine in table 2 is used in combination with CYP2C8 derivant (rifampicin), CYP2C8 wild type patient can suitably increase
Add using dosage, but sudden change patient is it is contemplated that be administered according to conventional description.
(4) CYP2C19: if child patient occur rs11188072, rs12767583, rs12768009, rs12769205,
rs12773342、rs145119820、rs17878459、rs17879685、rs17882687、rs17884712、
rs28399504、rs3758581、rs3814637、rs41291556、rs4244285、rs4917623、rs4986893、
rs4986894、rs55640102、rs55752064、rs55948420、rs56337013、rs57081121、rs5787121、
Rs58973490, rs6413438, rs6583954, rs72552267, rs72558184, rs72558185, rs72558186 are many
In state property one, when child patient uses the medicine in table 4, it is contemplated that reduce using dosage；If multiple polymorphism group occurs
Close or haplotype is positive, when child patient uses the medicine in table 4, it should be noted that monitoring, it is possible to decrease using dosage or change dressings.If going out
Existing rs12248560 polymorphism, when child patient uses the medicine in table 4, it is contemplated that increase using dosage.If said gene is many
State property is feminine gender, and child patient uses the medicine in table 4 medicine explanation to use routinely.But when in table 4 medicine with
CYP2C19 inhibitor (3. chloromycetin, cimetidine, felbamate, fluoxetine, fluvoxamine, indomethacin, ketoconazole, blue rope
Draw azoles, modafinil, omeprazole, oxcarbazepine, probenecid, ticlopidine, topiramate, pantoprazole, rabeprazole etc.) connection
When closing use, should suitably reduce using dosage, especially suffer from CYP2C19 gene pleiomorphism (not comprising rs12248560) child
In person.But when the medicine in table 4 and CYP2C19 derivant (carbamazepine, norethindrone, prednisone, rifampicin, pentobarbital etc.)
When being used in combination, CYP2C19 wild type patient can suitably increase using dosage, but sudden change (not comprising rs12248560) patient can
Consider to be administered according to conventional description.
(5) CYP2C9: if child patient occur rs10509680, rs1057909, rs1057910, rs1057911,
rs12572351、rs12782374、rs141011391、rs17847042、rs1799853、rs1934963、rs1934967、
rs1934968、rs1934969、rs2017319、rs2256871、rs28371685、rs28371686、rs2860905、
rs4086116、rs4917639、rs4918758、rs56165452、rs67807361、rs7089580、rs71486745、
rs72558187、rs72558188、rs72558189、rs72558190、rs72558191、rs7900194、rs9332094、
rs9332096、rs9332104、rs9332120、rs9332127、rs9332130、rs9332131、rs9332146、
In rs9332174, rs9332197, rs9332238, rs9332239 polymorphism one, child patient uses the medicine in table 5
Time, it is contemplated that reduce using dosage；If occurring, the combination of multiple polymorphism or haplotype are positive, and child patient uses the medicine in table 5
During thing, it should be noted that monitoring, it is possible to decrease using dosage or change dressings.If said gene polymorphism is feminine gender, child patient uses table 5
In medicine can routinely medicine explanation use.But when the medicine in table 5 and CYP2C9 inhibitor (amiodarone, fluconazol, non-promise
Bei Te, fluvastatin, fluvoxamine, isoniazid, lovastatin, paroxetine, Phenylbutazone/bute, probenecid, sertraline
Woods, sulfamethoxazole, sulfaphenazole, teniposide, voriconazole, trimethoprim, zafirlukast etc.) it is used in combination
Time, should suitably reduce using dosage, especially in CYP2C9 gene pleiomorphism child patient.But when in table 5 medicine with
When CYP2C9 derivant (rifampicin, quinalbarbitone) is used in combination, CYP2C9 wild type patient can suitably increase using dosage,
But sudden change patient is it is contemplated that be administered according to conventional description.
(6) CYP2D6: if child patient occur rs1065852, rs1080983, rs1080985, rs1080989,
rs1135840、rs1135824、rs138417770、rs16947、rs28360521、rs28371706、rs28371725、
rs28371733、rs35742686、rs367543000、rs371793722、rs3892097、rs5030655、rs5030656、
rs5030862、rs5030863、rs5030865、rs5030867、rs567606867、rs59421388、rs61736512、
In rs72549354, rs745746329, rs74966855, rs750996195, rs76088846, rs777560972 polymorphism
One, when child patient uses the medicine in table 6, it is contemplated that reduce using dosage；If multiple polymorphism combination or single occurs
Times type positive, when child patient uses the medicine in table 6, it should be noted that monitoring, it is possible to decrease using dosage or change dressings.If said gene
Polymorphism is feminine gender, and child patient uses the medicine in table 6 medicine explanation to use routinely.But when in table 6 medicine with
CYP2D6 inhibitor (amiodarone, BUP, celecoxib, chlorphenamine, chlorpromazine, cimetidine/cimetidine, sertraline
Woods, citalopram, clemastine, Clomipramine/clomipramine, ***e, diphenhydramine, doxepin, amycin/how soft ratio
Star, escitalopram/escitalopram, fluoxetine, Halofantrine, methotrimeprazine, metoclopramide, methadone, mibefradil, first
Oxygen Anfu woods, moclobemide, paroxetine, quinidine, duloxetine, terbinafine, perphenazine, atarax, ranitidine, fluorine
Piperidine alcohols, ritonavir, ticlopidine, tripelennamine etc.) when being used in combination, should suitably reduce using dosage, especially exist
In CYP2D6 gene pleiomorphism child patient.But when the medicine in table 6 joins with CYP2D6 derivant (dexamethasone, rifampicin etc.)
When closing use, CYP2D6 wild type patient can suitably increase using dosage, but sudden change patient is it is contemplated that give according to conventional description
Medicine.
(7) CYP2E1: if child patient occur rs1329149, rs2031920, rs2070672, rs2070673,
rs2070676、rs2249694、rs2249695、rs2480256、rs2515641、rs2515644、rs3813865、
rs3813867、rs4646976、rs55897648、rs6413419、rs6413420、rs6413432、rs72559710、
Rs743535, rs8192772, rs8192775, rs8192766, rs8192780, rs915906, rs915908, rs915909 are many
In state property one, when child patient uses the medicine in table 7, it is contemplated that reduce using dosage；If multiple polymorphism group occurs
Close or haplotype is positive, when child patient uses the medicine in table 7, it should be noted that monitoring, it is possible to decrease using dosage or change dressings.On if
Stating gene pleiomorphism and be feminine gender, child patient uses the medicine in table 7 medicine explanation to use routinely.But when in table 7
When medicine and CYP2E1 derivant (medicine such as ethanol, isoniazid) are used in combination, CYP2E1 wild type patient can suitably increase use
Dosage, but sudden change patient is it is contemplated that be administered according to conventional description.
(8) CYP3A4: if child patient occur rs1041988, rs12333983, rs12721627, rs12721629,
rs12721634、rs1851426、rs2242480、rs2246709、rs2687116、rs2740574、rs28371759、
rs3091339、rs3208361、rs3208363、rs35599367、rs3735451、rs45614732、rs4646437、
rs4646438、rs4646440、rs4986907、rs4986908、rs4986909、rs4986910、rs4986913、
rs4986914、rs4987161、rs55785340、rs55901263、rs55951658、rs56324128、rs67666821、
In rs67784355, rs6956344, rs72552799 polymorphism one, when child patient uses the medicine in table 8, can examine
Consider and reduce using dosage；If occurring, the combination of multiple polymorphism or haplotype are positive, when child patient uses the medicine in table 8, and should
Note monitoring, it is possible to decrease using dosage or change dressings.If said gene polymorphism is feminine gender, child patient uses the medicine in table 8
Thing can use routinely in medicine explanation.But as the medicine in table 8 and CYP3A4 inhibitor (indinavir, viracept see nelfinaivr, Li Tuona
Wei, Saquinavir, Ketek, Aprepitant, amiodarone, azithromycin, chloromycetin, cimetidine, ciprofloxacin, carat are mould
Element), diltiazem, erythromycin, fluconazol, fluvoxamine), gestodene, grapefruit juice, itraconazole, ketoconazole, meter Fei Si
Ketone, nefazodone, norfloxacin, norfluoxetine, mibefradil, verapamil, imatinib, voriconazole) when being used in combination,
Should suitably reduce using dosage, especially in CYP3A4 gene pleiomorphism child patient.But as the medicine in table 8 and CYP3A4
Derivant (efavirenz, nevirapine, barbiturate, carbamazepine, glucocorticoid, modafinil, oxcarbazepine,
Benzene bar ratio, appropriate rice that, phenytoin, rifampicin, Herba Hyperici perforati, troglitazone, pioglitazone, rifabutin etc.) when being used in combination,
CYP3A4 wild type patient can suitably increase using dosage, but sudden change patient is it is contemplated that be administered according to conventional description.
Case: lose with CYP3A4 according to CYP1A2, CYP2B6, CYP2C8, CYP2C19, CYP2C9, CYP2D6, CYP2E1
Pass polymorphism guiding children patient safety rational use of drug.
1. gather 1 example child patient peripheric venous blood.
2. extraction genomic DNA.
3. use CYP1A2, CYP2B6, CYP2C8, CYP2C19, CYP2C9, CYP2D6, CYP2E1 to examine with CYP3A4 gene
Test agent box, detects gene pleiomorphism.
4. testing result is: CYP1A2 wild type, CYP2B6 wild type, CYP2C8 wild type, CYP2C19rs4244285
Heterozygous mutation, CYP2C9 wild type, CYP2D6rs1065852 heterozygous mutation, CYP2E1 wild type, CYP3A4 wild type.
5. according to genotype this child patient CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2E1 and CYP3A4 enzyme
Activity is normal, the respective substrate of homergy (enzyme give from substrate see on), the reduction of CYP2C19 and CYP2D6 enzymatic activity, its
Metabolism substrate should be the most suitable minimizing.
Claims (4)
1. following gene pleiomorphism application in preparing guiding children patient accurate medication test kit:
(1) CYP1A2: comprise rs11636419, rs12720461, rs2069514, rs2069522, rs2069526,
rs2470890、rs2472299、rs2472300、rs2472304、rs28399424、rs35694136、rs3743484、
rs45564134、rs4646425、rs4646427、rs55889066、rs56276455、rs762551、rs72547516、
One or more combinations in rs72547517, rs72547513, rs72547511, rs72547515 polymorphism or haplotype；
(2) CYP2B6: comprise rs10403955, rs1042389, rs12721646, rs12721655, rs139801276,
rs186335453、rs2054675、rs2279343、rs2279344、rs2279345、rs281864907、rs28399499、
rs3211371、rs34097093、rs34223104、rs35303484、rs35979566、rs36118214、rs36079186、
rs371424910、rs373489637、rs3745274、rs3786547、rs45482602、rs4802101、rs4802104、
rs4803419、rs58425034、rs707265、rs7254579、rs7260329、rs8109848、rs8192709、
One or more combinations in rs8192719 polymorphism or the gene of haplotype；
(3) CYP2C8: comprise rs10509681, rs1058930, rs1058932, rs1113129, rs11572076,
rs11572080、rs11572103、rs11572177、rs1341162、rs1341164、rs17110453、rs193451、
rs1934951、rs1934953、rs1934980、rs2071426、rs2275622、rs3832694、rs66501115、
One or more combinations in rs7909236 polymorphism or haplotype；
(4) CYP2C19: comprise rs11188072, rs12248560, rs12767583, rs12768009, rs12769205,
rs12773342、rs145119820、rs17878459、rs17879685、rs17882687、rs17884712、
rs28399504、rs3758581、rs3814637、rs41291556、rs4244285、rs4917623、rs4986893、
rs4986894、rs55640102、rs55752064、rs55948420、rs56337013、rs57081121、rs5787121、
Rs58973490, rs6413438, rs6583954, rs72552267, rs72558184, rs72558185, rs72558186 are many
One or more combinations in state property or haplotype；
(5) CYP2C9: comprise rs10509680, rs1057909, rs1057910, rs1057911, rs12572351,
rs12782374、rs141011391、rs17847042、rs1799853、rs1934963、rs1934967、rs1934968、
rs1934969、rs2017319、rs2256871、rs28371685、rs28371686、rs2860905、rs4086116、
rs4917639、rs4918758、rs56165452、rs67807361、rs7089580、rs71486745、rs72558187、
rs72558188、rs72558189、rs72558190、rs72558191、rs7900194、rs9332094、rs9332096、
rs9332104、rs9332120、rs9332127、rs9332130、rs9332131、rs9332146、rs9332174、
One or more combinations in rs9332197, rs9332238, rs9332239 polymorphism or haplotype；
(6) CYP2D6: comprise rs1065852, rs1080983, rs1080985, rs1080989, rs1135840,
rs1135824、rs138417770、rs16947、rs28360521、rs28371706、rs28371725、rs28371733、
rs35742686、rs367543000、rs371793722、rs3892097、rs5030655、rs5030656、rs5030862、
rs5030863、rs5030865、rs5030867、rs567606867、rs59421388、rs61736512、rs72549354、
One or more in rs745746329, rs74966855, rs750996195, rs76088846, rs777560972 polymorphism
Combination or haplotype；
(7) CYP2E1: comprise rs1329149, rs2031920, rs2070672, rs2070673, rs2070676,
rs2249694、rs2249695、rs2480256、rs2515641、rs2515644、rs3813865、rs3813867、
rs4646976、rs55897648、rs6413419、rs6413420、rs6413432、rs72559710、rs743535、
In rs8192772, rs8192775, rs8192766, rs8192780, rs915906, rs915908, rs915909 polymorphism
One or more combinations or haplotype；
(8) CYP3A4: comprise rs1041988, rs12333983, rs12721627, rs12721629, rs12721634,
rs1851426、rs2242480、rs2246709、rs2687116、rs2740574、rs28371759、rs3091339、
rs3208361、rs3208363、rs35599367、rs3735451、rs45614732、rs4646437、rs4646438、
rs4646440、rs4986907、rs4986908、rs4986909、rs4986910、rs4986913、rs4986914、
rs4987161、rs55785340、rs55901263、rs55951658、rs56324128、rs67666821、rs67784355、
One or more combinations in rs6956344, rs72552799 polymorphism or haplotype.
2. preparing guiding children patient accurate medication test kit based on gene pleiomorphism, it is characterised in that in described test kit
Primer containing detecting following gene pleiomorphism:
(1) CYP1A2: comprise rs11636419, rs12720461, rs2069514, rs2069522, rs2069526,
rs2470890、rs2472299、rs2472300、rs2472304、rs28399424、rs35694136、rs3743484、
rs45564134、rs4646425、rs4646427、rs55889066、rs56276455、rs762551、rs72547516、
One or more combinations in rs72547517, rs72547513, rs72547511, rs72547515 polymorphism or haplotype；
(2) CYP2B6: comprise rs10403955, rs1042389, rs12721646, rs12721655, rs139801276,
rs186335453、rs2054675、rs2279343、rs2279344、rs2279345、rs281864907、rs28399499、
rs3211371、rs34097093、rs34223104、rs35303484、rs35979566、rs36118214、rs36079186、
rs371424910、rs373489637、rs3745274、rs3786547、rs45482602、rs4802101、rs4802104、
rs4803419、rs58425034、rs707265、rs7254579、rs7260329、rs8109848、rs8192709、
One or more combinations in rs8192719 polymorphism or the gene of haplotype；
(3) CYP2C8: comprise rs10509681, rs1058930, rs1058932, rs1113129, rs11572076,
rs11572080、rs11572103、rs11572177、rs1341162、rs1341164、rs17110453、rs193451、
rs1934951、rs1934953、rs1934980、rs2071426、rs2275622、rs3832694、rs66501115、
One or more combinations in rs7909236 polymorphism or haplotype；
(4) CYP2C19: comprise rs11188072, rs12248560, rs12767583, rs12768009, rs12769205,
rs12773342、rs145119820、rs17878459、rs17879685、rs17882687、rs17884712、
rs28399504、rs3758581、rs3814637、rs41291556、rs4244285、rs4917623、rs4986893、
rs4986894、rs55640102、rs55752064、rs55948420、rs56337013、rs57081121、rs5787121、
Rs58973490, rs6413438, rs6583954, rs72552267, rs72558184, rs72558185, rs72558186 are many
One or more combinations in state property or haplotype；
(5) CYP2C9: comprise rs10509680, rs1057909, rs1057910, rs1057911, rs12572351,
rs12782374、rs141011391、rs17847042、rs1799853、rs1934963、rs1934967、rs1934968、
rs1934969、rs2017319、rs2256871、rs28371685、rs28371686、rs2860905、rs4086116、
rs4917639、rs4918758、rs56165452、rs67807361、rs7089580、rs71486745、rs72558187、
rs72558188、rs72558189、rs72558190、rs72558191、rs7900194、rs9332094、rs9332096、
rs9332104、rs9332120、rs9332127、rs9332130、rs9332131、rs9332146、rs9332174、
One or more combinations in rs9332197, rs9332238, rs9332239 polymorphism or haplotype；
(6) CYP2D6: comprise rs1065852, rs1080983, rs1080985, rs1080989, rs1135840,
rs1135824、rs138417770、rs16947、rs28360521、rs28371706、rs28371725、rs28371733、
rs35742686、rs367543000、rs371793722、rs3892097、rs5030655、rs5030656、rs5030862、
rs5030863、rs5030865、rs5030867、rs567606867、rs59421388、rs61736512、rs72549354、
One or more in rs745746329, rs74966855, rs750996195, rs76088846, rs777560972 polymorphism
Combination or haplotype；
(7) CYP2E1: comprise rs1329149, rs2031920, rs2070672, rs2070673, rs2070676,
rs2249694、rs2249695、rs2480256、rs2515641、rs2515644、rs3813865、rs3813867、
rs4646976、rs55897648、rs6413419、rs6413420、rs6413432、rs72559710、rs743535、
In rs8192772, rs8192775, rs8192766, rs8192780, rs915906, rs915908, rs915909 polymorphism
One or more combinations or haplotype；
(8) CYP3A4: comprise rs1041988, rs12333983, rs12721627, rs12721629, rs12721634,
rs1851426、rs2242480、rs2246709、rs2687116、rs2740574、rs28371759、rs3091339、
rs3208361、rs3208363、rs35599367、rs3735451、rs45614732、rs4646437、rs4646438、
rs4646440、rs4986907、rs4986908、rs4986909、rs4986910、rs4986913、rs4986914、
rs4987161、rs55785340、rs55901263、rs55951658、rs56324128、rs67666821、rs67784355、
One or more combinations in rs6956344, rs72552799 polymorphism or haplotype.
3. based on gene pleiomorphism in the method preparing the accurate medication of guiding children patient, it is characterised in that described method is choosing
Select different gene detecting kits, detect CYP1A2, CYP2B6, CYP2C8, CYP2C19, CYP2C9, CYP2D6, CYP2E1
With CYP3A4 genetic polymorphism.
4. method as claimed in claim 3, it is characterised in that described CYP1A2, CYP2B6, CYP2C8, CYP2C19,
CYP2C9, CYP2D6, CYP2E1 include the following: with CYP3A4 genetic polymorphism
(1) CYP1A2: comprise rs11636419, rs12720461, rs2069514, rs2069522, rs2069526,
rs2470890、rs2472299、rs2472300、rs2472304、rs28399424、rs35694136、rs3743484、
rs45564134、rs4646425、rs4646427、rs55889066、rs56276455、rs762551、rs72547516、
One or more combinations in rs72547517, rs72547513, rs72547511, rs72547515 polymorphism or haplotype；
(2) CYP2B6: comprise rs10403955, rs1042389, rs12721646, rs12721655, rs139801276,
rs186335453、rs2054675、rs2279343、rs2279344、rs2279345、rs281864907、rs28399499、
rs3211371、rs34097093、rs34223104、rs35303484、rs35979566、rs36118214、rs36079186、
rs371424910、rs373489637、rs3745274、rs3786547、rs45482602、rs4802101、rs4802104、
rs4803419、rs58425034、rs707265、rs7254579、rs7260329、rs8109848、rs8192709、
One or more combinations in rs8192719 polymorphism or the gene of haplotype；
(3) CYP2C8: comprise rs10509681, rs1058930, rs1058932, rs1113129, rs11572076,
rs11572080、rs11572103、rs11572177、rs1341162、rs1341164、rs17110453、rs193451、
rs1934951、rs1934953、rs1934980、rs2071426、rs2275622、rs3832694、rs66501115、
One or more combinations in rs7909236 polymorphism or haplotype；
(4) CYP2C19: comprise rs11188072, rs12248560, rs12767583, rs12768009, rs12769205,
rs12773342、rs145119820、rs17878459、rs17879685、rs17882687、rs17884712、
rs28399504、rs3758581、rs3814637、rs41291556、rs4244285、rs4917623、rs4986893、
rs4986894、rs55640102、rs55752064、rs55948420、rs56337013、rs57081121、rs5787121、
Rs58973490, rs6413438, rs6583954, rs72552267, rs72558184, rs72558185, rs72558186 are many
One or more combinations in state property or haplotype；
(5) CYP2C9: comprise rs10509680, rs1057909, rs1057910, rs1057911, rs12572351,
rs12782374、rs141011391、rs17847042、rs1799853、rs1934963、rs1934967、rs1934968、
rs1934969、rs2017319、rs2256871、rs28371685、rs28371686、rs2860905、rs4086116、
rs4917639、rs4918758、rs56165452、rs67807361、rs7089580、rs71486745、rs72558187、
rs72558188、rs72558189、rs72558190、rs72558191、rs7900194、rs9332094、rs9332096、
rs9332104、rs9332120、rs9332127、rs9332130、rs9332131、rs9332146、rs9332174、
One or more combinations in rs9332197, rs9332238, rs9332239 polymorphism or haplotype；
(6) CYP2D6: comprise rs1065852, rs1080983, rs1080985, rs1080989, rs1135840,
rs1135824、rs138417770、rs16947、rs28360521、rs28371706、rs28371725、rs28371733、
rs35742686、rs367543000、rs371793722、rs3892097、rs5030655、rs5030656、rs5030862、
rs5030863、rs5030865、rs5030867、rs567606867、rs59421388、rs61736512、rs72549354、
One or more in rs745746329, rs74966855, rs750996195, rs76088846, rs777560972 polymorphism
Combination or haplotype；
(7) CYP2E1: comprise rs1329149, rs2031920, rs2070672, rs2070673, rs2070676,
rs2249694、rs2249695、rs2480256、rs2515641、rs2515644、rs3813865、rs3813867、
rs4646976、rs55897648、rs6413419、rs6413420、rs6413432、rs72559710、rs743535、
In rs8192772, rs8192775, rs8192766, rs8192780, rs915906, rs915908, rs915909 polymorphism
One or more combinations or haplotype；
(8) CYP3A4: comprise rs1041988, rs12333983, rs12721627, rs12721629, rs12721634,
rs1851426、rs2242480、rs2246709、rs2687116、rs2740574、rs28371759、rs3091339、
rs3208361、rs3208363、rs35599367、rs3735451、rs45614732、rs4646437、rs4646438、
rs4646440、rs4986907、rs4986908、rs4986909、rs4986910、rs4986913、rs4986914、
rs4987161、rs55785340、rs55901263、rs55951658、rs56324128、rs67666821、rs67784355、
One or more combinations in rs6956344, rs72552799 polymorphism or haplotype.
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