CN108192966A - For detecting the primer set of drug metabolic enzyme gene SNP site and its application - Google Patents

For detecting the primer set of drug metabolic enzyme gene SNP site and its application Download PDF

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CN108192966A
CN108192966A CN201810143897.1A CN201810143897A CN108192966A CN 108192966 A CN108192966 A CN 108192966A CN 201810143897 A CN201810143897 A CN 201810143897A CN 108192966 A CN108192966 A CN 108192966A
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CN108192966B (en
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张影
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Beijing Tianping Huapu Gene Technology Co ltd
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Abstract

The invention discloses for detecting the primer set of drug metabolic enzyme gene SNP site and its application, the primer set includes the amplimer pair and extension primer of 9 SNP sites of 7 drug metabolic enzyme related genes of human gene group DNA.Each site separately designs a pair of multiple pcr amplification primer object and a Single base extension primer, and using MALDI TOF MS（Matrix-Assisted Laser Desorption Ionization Time of Flight）Method detects sample to be tested SNP site parting.The present invention establishes a kind of detection method of the drug metabolic enzyme gene based on gene molecule parting, can in same reaction same time complete multiple SNP partings, precise and high efficiency and at low cost, its gene covered and site are related to children often with the 8 relevant metabolic enzyme genes of major class drug, are that covering surface is most complete in the genetic test product of children's safety medication so far.

Description

For detecting the primer set of drug metabolic enzyme gene SNP site and its application
Technical field
The present invention relates to technical field of gene detection, it particularly relates to for detecting drug metabolic enzyme gene SNP site Primer set and its application.
Background technology
Only more than 60 kinds of existing more than the 3500 kinds of medicine preparations in China, wherein children special-purpose.In this only more than 60 kinds of youngster In virgin medicine dedicated, there is also the situations that many mistakes use.Because of inappropriate medication, there are about 30000 children every year in China to be absorbed in The noiseless world, cause hepatic and renal function, nervous system equivalent damage be even more be difficult to count.In China, children poisoning by Year rises, and has reached 73% within 2014.Just there is 1 in every 8 children because adverse reaction occurs for inappropriate medication, cause liver kidney Function, nervous system injury.
The safety of medication is mainly related to its drug metabolism processes.If the accretion rate of drug in vivo reduces, it will Cause the accumulation of drug in vivo, so as to adverse reaction occur.And the metabolic rate of drug in vivo is mainly and drug metabolic enzyme Gene is related, the individual that drug metabolic enzyme gene morphs, and the metabolic rate of drug in vivo changes, and is that medicine occurs The major endogeneous of object adverse reaction.
The enzyme of drug metabolism is participated in liver microsomes enzymatic activity highest, is mainly catalyzed the generation of the exogenous materials such as drug It thanks, so also known as drug metabolic enzyme, abbreviation drug metabolizing enzyme.7 kinds of important hypotypes predominantly in CYP1, CYP2, CYP3：CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4, CYP3A5.The gene of individual are different, its enzymatic activity is caused to become Change, different metabolic ability of the Different Individual to same drug is shown as from phenotype.According to drug, accretion rate is fast in vivo Slowly can be divided into：1st, rapid inactivator；2nd, intermediate supersession type；3rd, slow inactivation；4th, super slow inactivation.If belonging to slow inactivation, Drug metabolic rate is more apparent than general population to be slowed down, it should be avoided using the drug or be replaced other active drugs, to reduce medicine The occurrence risk that drug accumulation caused by the bad metabolism of object is poisoned.
In drug metabolic enzyme gene detects correlative study, patent (CN200810208219.5) discloses a kind of drug generation Thank to related locus detecting method, patent (CN201610214241.5) discloses a kind of drug metabolic enzyme related gene SNP fluorescence Labeled complex amplification kit, the two patents have selected 5 SNP sites of 4 related genes respectively, and detection gene is not complete All key genes relevant with drug metabolism and mononucleotide polymorphism site are not covered in face；In addition, two above is special The method that profit and previous patent generally use all is fluorescence quantitative PCR method, and this method is suitable for the known SNP of detection 5 or so Site, when site increases, complicated for operation, time-consuming.
Invention content
For the above-mentioned technical problem in the relevant technologies, the present invention proposes to detect drug metabolic enzyme gene SNP site Primer set and its application, using MALDI-TOF MS methods, can in same reaction the same time complete 30 SNP points Type improves detection efficiency and reduces cost；By to children often with 8 major class drugs (antipyretic-antalgic class, respiratory system class, interior point Secrete system class, nervous system class, alimentary system class, cardiovascular system class, classes of anti-infective, antiallergy class) relevant drug enzyme Gene is detected, and understands metabolic capability of the children to inhomogeneity drug, and the reference frame of science is provided for rationally administration.
To realize the above-mentioned technical purpose, the technical proposal of the invention is realized in this way：
For detecting 7 drug metabolic enzymes that the primer set of drug metabolic enzyme gene SNP site includes human gene group DNA The PCR amplification primer pair of 9 SNP sites and Single base extension primer of related gene.
Further, 7 drug metabolic enzyme related genes of the human gene group DNA are in CYP1, CYP2, CYP3 7 The important hypotype of kind：CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4, CYP3A5.
Further, the SNP site is：Rs762551 sites on CYP1A2, the rs1057910 positions on CYP2C9 Point, rs4244285 the and rs4986893 sites on CYP2C19, the rs1065852 sites on CYP2D6, on CYP2E1 Rs3813867 and rs2031920 sites, the rs28371759 sites on CYP3A4, the rs776746 sites on CYP3A5.
Further, the primer set for being used to detect drug metabolic enzyme gene SNP site includes：
The PCR amplification primer sequence in the rs28371759 sites is the core shown in SEQ ID NO1 and SEQ ID NO2 Nucleotide sequence, Single base extension primer sequence are the nucleotide sequence shown in SEQ ID NO19；
The PCR amplification primer sequence in the rs4986893 sites is the core shown in SEQ ID NO3 and SEQ ID NO4 Nucleotide sequence, Single base extension primer sequence are the nucleotide sequence shown in SEQ ID NO20；
The PCR amplification primer sequence in the rs1057910 sites is the core shown in SEQ ID NO5 and SEQ ID NO6 Nucleotide sequence, Single base extension primer sequence are the nucleotide sequence shown in SEQ ID NO21；
The PCR amplification primer sequence in the rs1065852 sites is the core shown in SEQ ID NO7 and SEQ ID NO8 Nucleotide sequence, Single base extension primer sequence are the nucleotide sequence shown in SEQ ID NO22；
The PCR amplification primer sequence in the rs3813867 sites is the core shown in SEQ ID NO9 and SEQ ID NO10 Nucleotide sequence, Single base extension primer sequence are the nucleotide sequence shown in SEQ ID NO23；
The PCR amplification primer sequence in the rs776746 sites is the core shown in SEQ ID NO11 and SEQ ID NO12 Nucleotide sequence, Single base extension primer sequence are the nucleotide sequence shown in SEQ ID NO24；
The PCR amplification primer sequence in the rs762551 sites is the core shown in SEQ ID NO13 and SEQ ID NO14 Nucleotide sequence, Single base extension primer sequence are the nucleotide sequence shown in SEQ ID NO25；
The PCR amplification primer sequence in the rs4244285 sites is shown in SEQ ID NO15 and SEQ ID NO16 Nucleotide sequence, Single base extension primer sequence are the nucleotide sequence shown in SEQ ID NO26；
The PCR amplification primer sequence in the rs2031920 sites is shown in SEQ ID NO 17 and SEQ ID NO18 Nucleotide sequence, Single base extension primer sequence are the nucleotide sequence shown in SEQ ID NO27.
A kind of gene detecting kit, which is characterized in that it contains claim 1-4 any one of them for detecting medicine The primer set of object metabolic enzyme gene SNP site.
Further, the drug metabolic enzyme gene includes CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4、CYP3A5。
Further, the drug metabolic enzyme gene SNP site include rs762551 sites, rs1057910 sites, Rs4244285 sites, rs4986893 sites, rs1065852 sites, rs3813867 sites, rs2031920 sites, Rs28371759 sites, rs776746 sites.
Further, the primer set is prolonged by the amplimer pair and single base of SNP site each in claim 7 The object that extends forms.
Further, the kit genetic test result shows that cover children often includes antipyretic town with 8 major class drugs Pain class, respiratory system class, internal system class, nervous system class, alimentary system class, cardio-cerebrovascular class, classes of anti-infective, Antiallergy class drug.
Further, the kit genetic test is using human gene group DNA as sample, by primer set through multiplex PCR Sample SNP site parting is detected using Matrix-Assisted Laser Desorption Ionization Time of Flight method after amplification, it is described complete to draw The genetic test result of object multiplexed PCR amplification product shows sample medication metabolic capability.
Further, by being often detected to children with the relevant drug enzyme gene of 8 major class drugs, understand children couple The metabolic capability of inhomogeneity drug provides the reference frame of science for rationally administration.
Beneficial effects of the present invention：
1. update detection gene and site, compared with other patents detection gene more comprehensively；
2. improve existing common detection technique method, make that operation is easier, the cost-effective and time；
3. improving children's Irrational Use of Drugs present situation, precisely it is administered according to personal metabolic capability.
Specific embodiment
In order to facilitate the above-mentioned technical proposal for understanding the present invention, below by way of specific embodiment to the above-mentioned skill of the present invention Art scheme is described in detail, it is clear that described embodiment is only the reality of part of the embodiment of the present invention rather than whole Apply example.Based on the embodiments of the present invention, those of ordinary skill in the art's all other embodiments obtained belong to this hair The range of bright protection.
The establishment of 1 technical solution of embodiment
S1 designing technique routes：Determine the main component (table 1) of children's Common drugs, clearly with the relevant base of drug metabolism The deciphering (table 2) of cause and site SNP genotyping results and drug metabolic rate；
S2 establishes reaction system：Multiplexed PCR amplification primer (table 3) and extension primer (table 4) are designed, adjustment reactive component is dense Degree and reaction condition；
S2 analyzes sample：DNA is extracted, multiplexed PCR amplification, time-of-flight mass spectrometry (TOFMS) detection, interpretation of result and medication suggestion.
1 children's Common drugs of table and its main component
2 associated SNP positions parting of table and its drug metabolic rate
3 multiplexed PCR amplification primer sequence of table
4 Single base extension primer sequence of table
Sequence number SNP site Single base extension primer
19 rs28371759 CAGCTCTGTCCGATC
20 rs4986893 TGGCCTTACCTGGAT
21 rs1057910 TGGGGAGAAGGTCAA
22 rs1065852 CTGGGCTGCACGCTAC
23 rs3813867 TTCTTGGTTCAGGAGAG
24 rs776746 AGAGCTCTTTTGTCTTTCA
25 rs762551 AAGGGTGAGCTCTGTGGGC
26 rs4244285 CAGTAATTTGTTATGGGTTCC
27 rs2031920 TTAATTCATAGGTTGCAATTTT
2 sample extraction of embodiment and analysis
For the verification present invention for detecting the accuracy in detection and validity of the primer set of drug metabolic enzyme gene, select 10 samples carry out genetic test, and process is as follows：
A. saliva DNA is extracted：Using health saliva DNA extractions are carried out for century buccal swab genome DNA extracting reagent kit. A certain amount of absolute ethyl alcohol is added in GW1 and GW2 reagents.Take 500 μ L saliva samples from sampling pipe, add in 300 μ L GR, 20 μ L Proteinase K and 300 μ L GL shake mixing, and 56 DEG C of concussions are incubated 15min, add in 300 μ L absolute ethyl alcohols, concussion Mixing；The 750 μ L solution are added in the adsorption column of collecting pipe, 12000rpm centrifugation 1min abandon liquid；It is added in into adsorption column 400 μ L GW1,12000rpm centrifugation 1min, abandon liquid；400 μ L GW2,12000rpm centrifugation 1min are added in into adsorption column, are abandoned Liquid；12000rpm centrifuges 2min, and standing is dried；Adsorption column is placed in new 1.5mL centrifuge tubes, it is hanging to add in 40 μ L GE, it is quiet 5min is put, 12000rpm centrifugation 1min collect DNA solution, quality inspection, 4 DEG C of preservations.
B.PCR is expanded：The DNA of the step A samples to be tested extracted is added separately in 384 orifice plates, carries out multiplex PCR expansion Increase.It is added in each reacting hole, reaction system according to the reaction system (5 μ L) of multiplexed PCR amplification：
1 μ L of template DNA,
1 μ L of primer mix,
10 × Buffer, 0.5 μ L,
MgCl2(25mM) 0.4 μ L,
0.1 μ L of dNTP (25mM),
ddH21.8 μ L of O,
Hotstar (5U/ μ L) complements to 5 μ L.
Reaction system is tamping after preparing using PCR sealed membranes, prevents sample from evaporating, and shakes mixing, centrifugation；By sealing 384 orifice plates, which are placed in ABI9700 PCR instruments, to react, reaction condition：95 DEG C of pre-degeneration 2min (95 DEG C of 30s, 56 DEG C of 30s, 72 DEG C 1min) 45 cycles；72 DEG C of 5min, 4 DEG C of holdings；Pcr amplification product is obtained, centrifugation is spare.
C.SAP digests：Using Sequenom platforms matched reagent and operating procedure, sample to be tested SNP site parting is completed As a result.The pcr amplification product that will be obtained in step B is added to according to the SAP reaction systems (2 μ L) digested in each reacting hole, Reaction system：
0.17 μ L of SAP × Buffer,
SAP Enzyme (1U/ μ L) 0.3 μ L,
ddH2O 1.53μL；
Reaction system is tamping after preparing using PCR sealed membranes, prevents sample from evaporating, and shakes mixing, centrifugation；By sealing 384 orifice plates, which are placed in ABI9700 PCR instruments, to react, reaction condition：37 DEG C of 40min, 85 DEG C of 5min, 4 DEG C of holdings；Obtain alkalinity Phosphorylase treated PCR product, centrifugation are spare.
D. single base extension：Using Sequenom platforms matched reagent and operating procedure, sample to be tested SNP is completed Point genotyping result.By the PCR product after the alkaline phosphatase enzymatic treatment obtained in step C, according to single base extension system (2 μ L) is added in corresponding each reacting hole, reaction system：
0.94 μ L of extension primer mix,
0.2 μ L of Gold × Buffer,
0.2 μ L of Extension mix,
0.041 μ L of Iplex Enzyme,
ddH2O 0.619μL；
Reaction system is tamping after preparing using PCR sealed membranes, prevents sample from evaporating, and shakes mixing, centrifugation；By sealing 384 orifice plates, which are placed in ABI9700 PCR instruments, to react, reaction condition：94 DEG C of 30s, { 94 DEG C of 5s, (52 DEG C of 5s, 80 DEG C of 5s) 5 It is a internal to recycle } 40 outer loops, 72 DEG C of 3min, 4 DEG C of holdings；Single base extension product is obtained, centrifugation is spare.
E. purifying resin：Using Sequenom platforms matched reagent and operating procedure, sample to be tested SNP site parting is completed As a result.By 384 orifice plates of the single base extension product of step D, after sealed membrane of gently tearing, 16 μ L ddH are added in per hole2O；It takes Clean A4 paper is placed on it by 384 plates of 6MG, with the appropriate Purification Resin of small bale-out；With plastic plate, left and right is bulldozed purifying tree repeatedly Fat, compacting, makes every hole resin content uniform；The inversion of 384 plates is pressed on 384 plates of 6MG, two plates are exchanged, and 6MG plates are beaten upper 6MG backs make resin fall into 384 orifice plates equipped with single base extension product；After sealed membrane is sealed, 15rpm turns upside down Mixing 30min is fully purified.
F. chip point sample：384 orifice plates in step E are centrifuged, start MassARRAY Nanodispenser RS1000 Point sample instrument moves to the extension products after purifying resin on 384 hole SpectroCHIP chips；Chip after point sample uses MALDI-TOF is analyzed, and testing result is using TYPER4.0 softwares parting and exports result.
3 genetic test interpretation of result of embodiment
9 SNP site genetic test results (table 5) of 10 samples in embodiment 2 are analyzed, with reference to drug generation It thanks to enzyme gene associated SNP positions parting and its drug metabolic rate (table 2) provides rational use of medicines suggestion.
Table 5 drug metabolism related gene, 9 SNP site genotype
Site 1 2 3 4 5 6 7 8 9 10
rs1065852 A AG AG AG A G AG AG A AG
rs762551 A A AC C AC AC AC A A A
rs1057910 A A A A A A A A A A
rs4244285 G G G AG AG G AG AG G G
rs4986893 AG G G G G G AG G G G
rs28371759 A A A A A A A A A A
rs776746 C C CT C CT C C T CT C
rs3813867 G G CG G G G CG G G G
rs2031920 C C CT CT T C C C C CT
By table 5 as it can be seen that the genotype in 9 sites can be detected correctly, recall rate 100%.The amplification that the present invention designs is drawn Object and extension primer can detect 9 SNP sites in same reaction, for developing drug metabolic enzyme gene detection kit And guide safe medication.In terms of children's safety medication, genetic test of the invention can be appreciated that generation of the children to inhomogeneity drug It thanks to ability, the reference frame of science is provided for rationally administration.The gene and site covered in the present invention are related to and children's medicine Relevant 8 big categories of drugs of object is that covering surface is most complete in the genetic test product of children's safety medication so far.
The drug metabolism relationship of 4 people's drug metabolic enzyme gene of embodiment and medication suggestion
Fast metabolic pattern (EM), intermediate supersession type (IM), slow inactivation is generally presented in the activity of drug metabolic enzyme in crowd (PM) the phenomenon that being distributed.
CYP2D6 is responsible for the metabolism of a variety of drugs such as anticonvulsion class, calm anti-inflammatory type, endocrine class.
CYP1A2 accounted for for the 13% of the total P450 oxidizing ferment content of the liver generation for participating in many drugs, steroid hormone and induced pain object It thanks.The mutation in the site is the most functional and highest mutation of occurrence frequency, carries the individual of C allele, coffee Cause, phenacetin, theophylline, the accretion rate of paracetamol lower.
CYP2C9 participates in the metabolism of 6% drug in current clinical application.They are in two to the catalytic action of drug metabolism more State is distributed, i.e., fast metabolizer and poor metabolizer.There should be difference with poor metabolizer's dosage to being metabolized soon.
CYP2C19*2 causes montage to lack, and CYP2C19*3 is mutated for terminator codon, and homozygotic individual enzymatic activity is only The 4~6% of wild-type homozygote genotype individuals.CYP2C9 genetic polymorphisms lead to its Enzyme activities, so as to cause drug Metabolism race and individual difference phenomenon.75~85% poor metabolizer is caused by CYP2C19*2 in the crowd of east, and about 20~25% Poor metabolizer caused by CYP2C19*3.
CYP3A4 is a kind of main cytochrome P 450 enzymes in human liver, accounts for about adult human liver CYP450 enzyme total amounts 25%, liver cell, liver epithelial duct are distributed mainly on, is liver drug enzymes most in liver, metabolism is participated in about in enteron aisle 90% drug, clinically about 50% drug is via the metabolism of CYP3A4 enzymes.
The SNP of CYP3A5 can lead to CYP3A5 mRNA aberrant splicings, and terminator codon is caused to shear CYP3A5 eggs too early In vain, so as to which it be made to lose the activity of enzyme, therefore CYP3A5*3 homozygotic individuals liver and enteron aisle CYP3A5 protein expressions and activity It is remarkably decreased.CYP3A5 participates in the metabolism of tacrolimus, midazolam, dapsone, cortisone, the Buddhist nun luxuriant and rich with fragrance ground a variety of drugs of equality.
The substrate of CYP2E1 is more, and wherein most is precarcinogen and preceding poisonous substance, and small part is drug.Because of its activity Body difference is apparent, therefore has certain influence to the drug therapy effect and adverse reaction of Different Individual.CYP2E1 is oxidation of ethanol A kind of main constitutive enzyme in system, while may participate in the generation of the hydrophobic toxicant of more than 80 kinds of low molecule, carcinogen, drug It thanks, it makes these low molecular compounds be converted into compared with the stronger metabolite of parent compound chemical reaction.CYP2E1 contents Averagely account for the 6.6% of human liver's system.Main metabolic Chlorzoxazone；Also paracetamol, dapsone, aniline, second are metabolized The fluoride of alcohol and general anesthetic.
Medication suggestion (example)：Paracetamol is the main component of the common analgesic-antipyretic of children, there is maincenter god It is children's Common drugs pediatric paracetamol granule (children's crack), (children are safe for acetaminophen compound suspension through antipyretic function Promise) etc. drugs main component.The medicine of paracetamol in vivo is CYP1A2 and CYP2E1 for enzyme, the result of genetic test It was found that there are unfavorable variations on two genes by subject 3 and subject 4 in 3 table 5 of embodiment, it is the slow of paracetamol Metabolizer is aggravated using the adverse reaction of acetparaminosalol phenol agents；Similarly ntipyretic analgesic medicine ingredient brufen is main Metabolic enzyme is CYP2C9, and the two metabolic enzyme gene is normal, so two subjects in administration, preferred should contain brufen Antipyretics object reduces the use of paracetamol.
The foregoing is merely illustrative of the preferred embodiments of the present invention, is not intended to limit the invention, all essences in the present invention With within principle, any modification, equivalent replacement, improvement and so on should all be included in the protection scope of the present invention god.
SEQUENCE LISTING
<110>Beijing balance Yong Da developments in science and technology Co., Ltd
<120>For detecting the primer set of drug metabolic enzyme gene SNP site and its application
<130> 2018.02
<160> 27
<170> PatentIn version 3.3
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<211> 16
<212> DNA
<213> Artificial
<223>Rs1065852 Single base extension primers
<400> 22
ctgggctgca cgctac 16
<210> 23
<211> 17
<212> DNA
<213> Artificial
<223>Rs3813867 Single base extension primers
<400> 23
ttcttggttc aggagag 17
<210> 24
<211> 19
<212> DNA
<213> Artificial
<223>Rs776746 Single base extension primers
<400> 24
agagctcttt tgtctttca 19
<210> 25
<211> 19
<212> DNA
<213> Artificial
<223>Rs762551 Single base extension primers
<400> 25
aagggtgagc tctgtgggc 19
<210> 26
<211> 21
<212> DNA
<213> Artificial
<223>Rs4244285 Single base extension primers
<400> 26
cagtaatttg ttatgggttc c 21
<210> 27
<211> 22
<212> DNA
<213> Artificial
<223>Rs2031920 Single base extension primers
<400> 27
ttaattcata ggttgcaatt tt 22

Claims (10)

1. for detecting the primer set of drug metabolic enzyme gene SNP site, it is characterised in that：7 including human gene group DNA The PCR amplification primer pair of 9 SNP sites and Single base extension primer of drug metabolic enzyme related gene.
2. the primer set according to claim 1 for being used to detect drug metabolic enzyme gene SNP site, which is characterized in that 7 drug metabolic enzyme related genes of the human gene group DNA are 7 kinds of important hypotypes in CYP1, CYP2, CYP3： CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4, CYP3A5.
3. the primer set according to claim 2 for being used to detect drug metabolic enzyme gene SNP site, which is characterized in that 9 SNP sites are：Rs762551 sites on CYP1A2, the rs1057910 sites on CYP2C9, on CYP2C19 Rs4244285 and rs4986893 sites, the rs1065852 sites on CYP2D6, rs3813867 on CYP2E1 and Rs2031920 sites, the rs28371759 sites on CYP3A4, the rs776746 sites on CYP3A5.
4. the primer set according to claim 3 for being used to detect drug metabolic enzyme gene SNP site, it is characterised in that:
The PCR amplification primer sequence in the rs28371759 sites is the nucleotide shown in SEQ ID NO1 and SEQ ID NO2 Sequence, Single base extension primer sequence are the nucleotide sequence shown in SEQ ID NO19;
The PCR amplification primer sequence in the rs4986893 sites is the nucleotide shown in SEQ ID NO3 and SEQ ID NO4 Sequence, Single base extension primer sequence are the nucleotide sequence shown in SEQ ID NO20;
The PCR amplification primer sequence in the rs1057910 sites is the nucleotide shown in SEQ ID NO5 and SEQ ID NO6 Sequence, Single base extension primer sequence are the nucleotide sequence shown in SEQ ID NO21;
The PCR amplification primer sequence in the rs1065852 sites is the nucleotide shown in SEQ ID NO7 and SEQ ID NO8 Sequence, Single base extension primer sequence are the nucleotide sequence shown in SEQ ID NO22;
The PCR amplification primer sequence in the rs3813867 sites is the nucleotide shown in SEQ ID NO9 and SEQ ID NO10 Sequence, Single base extension primer sequence are the nucleotide sequence shown in SEQ ID NO23;
The PCR amplification primer sequence in the rs776746 sites is the nucleotide shown in SEQ ID NO11 and SEQ ID NO12 Sequence, Single base extension primer sequence are the nucleotide sequence shown in SEQ ID NO24;
The PCR amplification primer sequence in the rs762551 sites is the nucleotide shown in SEQ ID NO13 and SEQ ID NO14 Sequence, Single base extension primer sequence are the nucleotide sequence shown in SEQ ID NO25;
The PCR amplification primer sequence in the rs4244285 sites is the nucleosides shown in SEQ ID NO15 and SEQ ID NO16 Acid sequence, Single base extension primer sequence are the nucleotide sequence shown in SEQ ID NO26;
The PCR amplification primer sequence in the rs2031920 sites is the nucleosides shown in SEQ ID NO17 and SEQ ID NO18 Acid sequence, Single base extension primer sequence are the nucleotide sequence shown in SEQ ID NO27.
5. a kind of gene detecting kit, which is characterized in that it contains claim 1-4 any one of them for detecting drug The primer set of metabolic enzyme gene SNP site.
6. as a kind of gene detecting kit described in claim 5, it is characterised in that:The drug metabolic enzyme gene includes CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4, CYP3A5.
7. as a kind of gene detecting kit described in claim 5, it is characterised in that:The drug metabolic enzyme gene SNP Site include rs762551 sites, rs1057910 sites, rs4244285 sites, rs4986893 sites, rs1065852 sites, Rs3813867 sites, rs2031920 sites, rs28371759 sites, rs776746 sites.
8. as a kind of gene detecting kit described in claim 5, it is characterised in that:The primer set is by claim The amplimer pair of each SNP site and Single base extension primer composition in 7.
9. as a kind of gene detecting kit described in claim 5, it is characterised in that:The kit genetic test result The normal metabolic capability with 8 major class drugs of children is covered in display, including antipyretic-antalgic class, respiratory system class, internal system class, god Through system class, alimentary system class, cardio-cerebrovascular class, classes of anti-infective, antiallergy class drug.
10. as a kind of gene detecting kit described in claim 5, which is characterized in that the kit genetic test side Method is：Using human gene group DNA as sample, primer set is flown after multiplexed PCR amplification using Matrix Assisted Laser Desorption ionization Row time mass spectrum method detects sample SNP site parting, according to the medicament metabolism ability of the corresponding SNP site of genotype judgement sample.
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