Genetic polymorphisms and phenotypic analysis of drug-metabolizing enzyme CYP2C19 in a Li Chinese population

CYP2C19 is a highly polymorphic gene and CYP2C19 enzyme results in broad inter-individual variability in response to certain clinical drugs, while little is known about the genetic variation of CYP2C19 in Li Chinese population. The aim of this study was to identify different CYP2C19 mutant alleles and determine their frequencies, along with genotype frequencies, in the Li Chinese population. We used DNA sequencing to investigate promoter, exons, introns, and 3’UTR of the CYP2C19 gene in 100 unrelated healthy Li individuals from Hainan Province, China. We also used SIFT and PolyPhen-2 to predict the protein function of the non-synonymous mutation in CYP2C19 coding regions. We identified 22 different CYP2C19 polymorphisms in the Li Chinese population, including three novel variants (-254A > G, 17807T > C and 58025C > T). The allele frequencies of CYP2C19*1A, *1B, *2A and *3A were 50%, 24%, 24.5%, and 1.5%, respectively. The most common genotype combinations were *1A/*1B (48%) and *1A/*2A (49%). Additionally, the mutation Ala161Pro was predicted to be intolerant and possibly damaging by SIFT and PolyPhen-2, respectively. Our results shed new light on CYP2C19 polymorphisms in Li individuals, which may help to optimize pharmacotherapy effectiveness by providing personalized medicine to this ethnic group.     

Adverse drug reaction monitoring in Jena: Relevance of polymorphic drug metabolizing enzymes for inducing adverse drug reactions

Inter-subject variability in therapeutic drug response and drug toxicity is a major problem in clinical practice. In this field genetic polymorphisms of drug metabolizing enzymes play an important role. In a multicenter study supported by the German Federal Institute for Drugs and Medical Devices (BfArM, Z 12.01-68502-201) adverse drug reactions (ADRs) leading to hospital admission to departments of internal medicine have been registered and evaluated. The aim of the presented part of the study was to look for evident differences in genotypes for polymorphic drug metabolizing enzymes between adverse drug reaction cases and controls. All cases found in the local area – Jena and Weimar – were genotyped for N-acetyl-transferase 2 (NAT2), cytochrom P450 (CYP) 2D6 and 2C19 in comparison to a control population of the same region. The investigation on genotype was carried out for about 2 years (2000–2002). 254 blood samples from patients of the ADR study were analyzed. The genotype of drug metabolizing enzymes was determined by means of polymerase chain reaction using allel specific primers or restriction enzyme analysis. Within all ADRs cases genotyped, no exceptional frequencies for slow acetylators or poor metabolizers (PM) of CYP2D6 or CYP2C19 were found. About 65% of the individuals with ADR genotypically displayed a slow acetylator state. 6.3% PM for CYP2D6, including CYP2D6*3, *4 and *6 alleles, and 2.0% PM frequency for CYP2C19 (*2) have been found in ADR cases. A direct connection between PM genotype and the ADR observed may be assumed only in few of them. Further investigations on genotype and ADR-associated drugs require a much larger sample of patients to obtain more data allowing to focus an association on specific drugs, ADR and polymorphisms genotype of drug metabolizing enzymes might be useful.     

Single nucleotide polymorphisms and haplotype frequencies of CYP3A5 in a Japanese population

In order to identify single nucleotide polymorphisms (SNPs) and haplotype frequencies of CYP3A5 in a Japanese population, we sequenced the proximal promoter region, all exons, and the surrounding intronic regions using genomic DNA from 187 Japanese subjects. Thirteen SNPs, including seven novel ones: 13108T>C, 16025A>G, 16903A>G, 16993C>G, 27448C>A, 29782A>G, and 31551T>C (A of the translational start codon of GenBank Accession # NG_000004.2 is numbered 1 according to the CYP Allele Nomenclature), were identified. The most common SNP was 6986A>G (key SNP for CYP3A5*3), with a 0.759 frequency. Two novel SNPs, 29782A>G (I456V) and 31551T>C (I488T), as well as 12952T>C (*5 marker) were found, but these alterations were always associated with the *3A marker SNPs, 6986A>G and 31611C>T. Using these 13 SNPs, haplotype analysis was performed and five novel *1 haplotypes (subtypes) (*1e to *1i) and six novel *3 haplotypes (subtypes) (*3d to *3i) were identified. Our findings suggest that CYP3A5*3 is the major defective allele and that other functional exonic SNPs are rare in the Japanese.     

Distribution of polymorphisms in the CYP2C9 gene and CYP2C19/CYP2C9 haplotypes among Venezuelan populations

Background: Polymorphisms with decreased enzyme activity of their gene products have been reported in region CYP2C with population variations in haplotype structure.

Aim: To estimate the allelic and genotypic frequencies of variants CYP2C9*2 and CYP2C9*3 and of CYP2C9/CYP2C19 haplotypes in Venezuelan populations.

Subjects and methods: Six hundred and thirty-four individuals from nine admixed populations (AP) and the Warao indigenous group were studied. Allelic frequencies, linkage disequilibrium and genetic distances for haplotypes were calculated and compared within Venezuela and with data available in the literature.

Results: Heterogeneity in the distribution of CYP2C9 alleles and CYP2C9/CYP2C19 haplotypes among the AP and the Warao was observed. The joint frequency of haplotypes, with at least one non-functional variant, shows values in AP between 21–41%, while in Warao it reaches 5%. The haplotype that includes the Asian and rare Latin America CYP2C19*3 allele was detected in most AP and in Warao. Pairwise Fst values showed that the Warao was an outlier compared with the AP, while these are closer to European-derived populations. No significant correlation was found between haplotype frequencies and admixture.

Conclusions: These results support the need to understand the distribution of genomic biomarkers related to the metabolism of drugs, for planning national public health strategies.     

High resolution melting method to detect single nucleotide polymorphism of VKORC1 and CYP2C9

Single nucleotide polymorphisms (SNPs) of VKORC (1173T/C, rs9934438) and CYP2C9 (1075A/C, rs1057910) are major contributory factors on the sensitivity of warfarin in Chinese. Analysis of the two genomic loci could help warfarin treatment individual from bleeding or thrombosis events. An assay with the advantages of simplicity, speed, high sensitivity and low cost for genotyping is calling for clinical laboratories. High resolution method (HRM) meets these callings, but no study with large sample tested its performance in genotyping of rs9934438 and rs1057910. In this study, we identified polymorphisms of rs9934438 and rs1057910 in 255 unrelated Chinese heart valve replacement patients of Han ethnic group from West China Hospital. The two genomic loci were genotyped by HRM using LightCycler® 480 High Resolution Melting Master on LightCycler® 480 Real-Time PCR instruments (Roche Diagnostics), and all amplified PCR products were sent for direct DNA sequencing. The genotyping of rs1057910 between HRM and sequencing showed perfect 100% concordance. While the concordance of rs9934438 between HRM and sequencing was 99.2%. Unexpected mutation interfered genotyping results of HRM when genotyping rs9934438. HRM is a valuable technique for genotype detection of rs9934438 and rs1057910 to assess individual sensitivity to warfarin, where DNA sequencing is added inevitably sometimes.     

等位基因特异荧光PCR法检测CYP2C19基因型

目的了解人群CYP2C19基因型的分布,评价等位基因特异荧光PCR法检测CYP2C19基因型。方法等位基因特异荧光PCR法和金标准Sanger DNA直接测序法检测356名供者外周血CYP2C19基因型,实验采用同步盲法。结果 CYP2C19*1/*1型、CYP2C19*1/*2型、CYP2C19*2/*3型、CYP2C19*3/*3型、CYP2C19*2/*2型及CYP2C19*1/*3型的频率分布:使用PCR荧光法检测时分别为46.6%(166/356)、33.2%(118/356)、2.0%(7/356)、0.8%(3/356)、10.7%(38/356)及6.7%(24/356);采用DNA测序法时分别为46.3%(165/356)、33.4%(119/356)、2.0%(7/356)、0.8%(3/356)、11.0%(39/356)及6.5%(23/356)。两种方法检测CYP2C19基因型具有一致性(P=0.392),且一致性较好(Kappa=0.987);两种方法基因型检测结果一致率为99.2%。结论为保障医疗安全,临床需开展CYP2C19基因型检测;等位基因特异荧光PCR法检测CYP2C19基因型简便可靠。     

Novel and established CYP2A6 alleles impair in vivo nicotine metabolism in a population of Black African descent

Cytochrome P450 2A6 (CYP2A6) is a human enzyme best known for metabolizing tobacco-related compounds, such as nicotine, cotinine (COT), and nitrosamine procarcinogens. CYP2A6 genetic variants have been associated with smoking status, cigarette consumption, and tobacco-related cancers. Our objective was to functionally characterize four nonsynonymous CYP2A6 sequence variants with respect to their haplotype, allele frequency, and association with in vivo CYP2A6 activity. In vivo, nicotine was administered orally to 281 volunteers of Black African descent. Blood samples were collected for kinetic phenotyping and CYP2A6 genotyping. In vitro, nicotine C-oxidation catalytic efficiencies of heterologously expressed variant enzymes were assessed. The four uncharacterized sequence variants were found in seven novel alleles CYP2A6(*)24A&B ; (*)25, (*)26, (*)27, and *28A&B, most were associated with impaired in vivo CYP2A6 activity. Nicotine metabolism groupings, based on the in vivo data of variant alleles, were created. Mean trans-3'-hydroxycotinine/cotinine (3HC/COT) differed (P<0.001) between normal (100%), intermediate (64%), and slow (40%) groups. Systemic exposure to nicotine following oral administration also differed (P<0.001) between normal (100%), intermediate (139%), and slow (162%) metabolism groups. In addition, alleles of individuals with unusual phenotype-genotype relationships were sequenced, resulting in the discovery of five novel uncharacterized alleles and at least one novel duplication allele. A total of 7% of this population of Black African descent had at least one of the eight novel characterized alleles and 29% had at least one previously established allele. These findings are important for increasing the accuracy of association studies between CYP2A6 genotype and behavioral, disease, or pharmacological phenotypes.     

Combination Analysis in Genetic Polymorphisms of Drug-Metabolizing Enzymes CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A5 in the Japanese Population

The Cytochrome P450 is the major enzyme involved in drug metabolism. CYP enzymes are responsible for the metabolism of most clinically used drugs. Individual variability in CYP activity is one important factor that contributes to drug therapy failure. We have developed a new straightforward TaqMan PCR genotyping assay to investigate the prevalence of the most common allelic variants of polymorphic CYP enzymes CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A5 in the Japanese population. Moreover, we focused on the combination of each genotype for clinical treatment. The genotype analysis identified a total of 139 out of 483 genotype combinations of five genes in the 1,003 Japanese subjects. According to our results, most of subjects seemed to require dose modification during clinical treatment. In the near future, modifications should be considered based on the individual patient genotype of each treatment.     

Genotype-Phenotype Analysis of CYP2C19 in Healthy Saudi Individuals and its Potential Clinical Implication in Drug Therapy

CYP2C19 is a cytochrome P450 enzyme, which is involved in the metabolism of some clinically important medications and is encoded by a highly polymorphic gene. There is no available data on the distribution of the CYP2C19 *4 and *17 mutant alleles in the Saudi Arabian population. The aim of the study was to determine different CYP2C19 mutant allele (*2, *4 and *17) frequencies in healthy Saudi subjects and to determine genotype frequencies for these mutations. The CYP2C19 genotypes were then classified into phenotypes. Result: In 201 adults of Saudi ethnicity, the allele frequencies were CYP2C19*1 (62.9%), *17 (25.7%), *2 (11.2%) and *4 (0.2%). The most prevalent genotype combinations were CYP2C19 *1/*1 (40.3%) and *1/*17 (30.4%). The distribution of CYP2C19 phenotypes was divided into extensive metabolizers (EM) 77.6%, intermediate metabolizers (IM) 14.9%, ultra-rapid metabolizers (UM) 7% and poor metabolizers (PM) 0.4%. This finding has important clinical implications for the use of CYP2C19 metabolized medications in the Saudi population and further studies are needed.     

A new,rapid and robust genotyping method for CYP2C9 and MDR1

Single nucleotide polymorphisms (SNPs) can significantly affect human phenotypes. Detection of allelic variant carriers has become a major goal for clinical pharmacologists in order to study phenotype-genotype relationships. However, there is a crucial need for rapid, and validated pharmacogenetic tests. The aim of the study was to validate a new fluorescence PCR strategy for cytochrome P450 2C9 (CYP2C9) and multidrug resistance gene (MDR1) genotyping. Results of CYP2C9 and MDR1 genotypes determined with reference techniques were compared to those obtained by allelic discrimination assays employing fluorescent TaqMan probes. Sixteen subjects carrying CYP2C9*2 and CYP2C9*3 allelic variants (heterozygous and homozygous) previously identified by sequencing and 55 subjects previously genotyped for MDR1 exon 26 (C3435T) SNP by conventional PCR-RFLP were genotyped with fluorescent PCR. Fluorescent PCR gave 100 % accuracy with the results obtained with reference genotyping strategies for each of the 3 SNPs. Genotyping results with fluorescent PCR repeated on three consecutive occasions remained constant over time for each of the 3 SNPs. Allelic discrimination assays based on fluorescent PCR gave entire satisfaction for CYP2C9 and MDR1 genotyping. This reliable genotyping strategy can be easily used in clinical practice and should be further developed for additional SNPs identification.     

Ah receptor, CYP1A1, CYP1A2 and CYP1B1 gene polymorphisms are not involved in the risk of recurrent pregnancy loss

The etiology of recurrent pregnancy loss (RPL) remains unclear, but it may be related to a possible genetic predisposition together with involvement of environmental factors. We examined the relation between RPL and polymorphisms in four genes, human aryl hydrocarbon (Ah) receptor, cytochrome P450 (CYP) 1A1, CYP1A2 and CYP1B1, which are involved in the metabolism of a wide range of environmental toxins and carcinogens. All cases and controls were women resident in Sapporo, Japan and the surrounding area. The Ah receptor, CYP1A1, CYP1A2 and CYP1B1 genotypes were assessed in 113 Japanese women with recurrent pregnancy loss (RPL) and 203 ethnically matched women experiencing at least one live birth and no spontaneous abortion (control). No significant differences in Ah receptor, CYP1A1, CYP1A2 and CYP1B1 genotype frequencies were found between the women with RPL and the controls [Ah receptor: Arg/Arg (reference); Arg/Lys and Lys/Lys, odds ratio (OR)=0.67; 95% confidence interval (CI)=0.40-1.11, CYP1A1: m1m1 (reference); m1m2 and m2m2, OR = 0.86; 95% CI = 0.53-1.40, CYP1A2: C/C and C/A (reference); A/A, OR = 1.16; 95% CI = 0.71-1.88, CYP1B1: Leu/Leu (reference); Leu/Val and Val/Val, OR = 1.18; 95% CI = 0.68-2.02]. The present study suggests that the Ah receptor, CYP1A1, CYP1A2 and CYP1B1 gene polymorphisms are not major genetic regulators in RPL.     

Prevalence of MDR1 C3435T and CYP2B6 G516T polymorphisms among HIV-1 infected South African patients

Data on genetic polymorphisms associated with response to anti-HIV drugs has accumulated over the years. Information on how polymorphisms influence drug metabolism and transport to target sites is important in guiding dosage or selection of appropriate alternative therapies. This study determined the frequency of MDR1 C3435T and CYP2B6 G516T polymorphisms associated with the transport and metabolism of efavirenz and nevirapine, in a population of South African HIV infected patients. In addition, association of polymorphisms with immunologic and virologic factors was investigated. A 207bp of MDR1 exon 26 and a 161bp of CYP2B6 exon 4 were obtained from patients by polymerase chain reaction. Analysis of population-based sequences of MDR1 revealed a frequency of 89% and 11% of C and T alleles respectively (n=197; X^{2} = 0.974; p=0.324). Restriction fragment length polymorphism (RFLP) analysis of the CYP2B6 gene revealed a prevalence of 9.5% of GG, 78.4% of GT and 12.1% of TT genotype (n= 199; X^{2} = 65.204; p=0.00). There was no significant difference between immune recovery and decline in viral load (n=53), with genotype after repeated calculations of analysis of variance (ANOVA).     

CYP3A5基因的多态性及其临床意义的研究

目的 了解中国人群中细胞色素P450 3A5基因CYP3A5的多态性及其基因型与临床功能之间的关联。方法 应用变性高效液相色谱技术对180份样本进行基因变异的检测，并经测序验证；以免疫荧光偏振技术监测12例造血干细胞移植患者环孢素（cyclospofin A，CsA）血浓度，数据经统计学软件分析和处理。结果 180份样本中，共检测出1种等位基因即CYP3A5＊3，其频率为76．1％（274／360）；3种基因型，即纯合子CYP3A5＊1／＊1 10份，占总数的5．6％；杂合子CYP3A5＊1／＊3 66份，占总数的36．7％；纯合子CYP3A5＊3／＊3 104份，占总数的57．8％。12例造血干细胞移植患者中检测出两种基因型，即CYP3A5＊1／＊1 2例和CYP3A5＊l／＊3 10例。CYP3A5＊1／＊ l患者外周血均一化后的CsA浓度与CYP3A5＊1／＊3相比较，前者谷浓度C0较后者低，相差2．3～6．6倍，差异有统计学意义（P〈0．01）；服药后2 h峰值C2亦较后者低，相差1．4～3．8倍，同样差异有统计学意义（P〈0．01）。结论 CYP3A5＊3是中国人群中最主要的多态性，CYP3A5基因型与造血干细胞移植患者血中CsA浓度紧密关联，CYP3A5＊1／＊1比CYP3A5＊1／＊3需要更大剂量的CsA以维持相同的血浓度。应用变性高效液相色谱对CYP3A5进行基因型分型，可以预测患者CYP3A5的功能，进而预测其CsA的需求量，使临床应用CsA更加安全有效和个体化。     

温州地区汉族正常人群CYP1A2基因多态性分布特征

目的检测CYP1A2基因多态性在温州地区汉族正常人群的分布特征。方法采用聚合酶链反应（PCR）产物直接测序法检测108例随机血液样本DNA中CYP1A2基因序列单核苷酸多态性位点（SNP）的分布。对检测到的3个多态位点2159G〉A、3613T〉C、5347C〉T,进一步采用PCR技术分析472例正常人位点的基因型频率和等位基因频率。结果 （1）2159 G〉A位点：G和A等位基因的频率分别为93.8%,6.2%,GG、GA、AA基因型频率分别为87.7%、12.1%、0.2%（χ2=0.325,P〉0.05）;（2）3613 T〉C位点：T和C等位基因的频率分别为97.9%、2.3%,TT、TC、CC基因型频率分别为95.3%、4.4%、0.3%（χ2=0.298,P〉0.05）;（3）5347 C〉T位点：C和T等位基因的频率分别为87.9%、12.1%。CC、CT、TT基因型分布频率分别为77.8%、20.3%、1.9%（χ2=0.742,P〉0.05）;（4）2159 G〉A、5347 C〉T组成的单倍型频率为3.2%。结论温州地区汉族正常人群CYP1A2基因存在2159G〉A、3613T〉C、5347C〉T多态位点。     

The ADH3*2 and CYP2E1 c2 alleles increase the risk of alcoholism in Mexican American men

To identify the association between the polymorphisms of genes encoding alcohol metabolizing enzymes and alcoholism, the alcohol dehydrogenase 2 (ADH2), alcohol dehydrogenase 3 (ADH3), aldehyde dehydrogenase 2 (ALDH2), and cytochrome P450 2E1 (CYP2E1) genes were studied in 101 male Mexican American alcoholics. One hundred and four Mexican American nonalcoholic males served as controls. The allele frequency of ADH2*2 (4.3%) and ALDH2*2 (0%), which are considered as protective alleles against alcohol drinking, is very low in Mexican Americans and no association is found between these alleles and alcohol dependence. A strong association was found between ADH3 genotype and alcoholism; the percentage of subjects who carry the ADH3*2 allele was significantly higher in alcoholics (64.4%) than controls (50%). Association was also found between the CYP2E1 RsaI c2 allele and alcohol dependence; the percentage of subjects who carry the RsaI c2 allele was significantly higher in alcoholics (34.7%) than in nonalcoholics (22.1%). The subjects whose alcohol drinking onset age is younger than 25 have much higher CYP2E1 c2 allele frequency than those whose alcohol drinking onset age is older than 25 (22.1% vs 15.7%). Among 101 alcoholics, only 18 subjects carry neither ADH3*2 nor CYP2E1 c2 alleles. For those subjects who have an ADH*1/*1 background, a strong association is found between CYP2E1 RsaI/DraI genotype and alcoholism; the CYP2E1 RsaI c2 and DraI C allele frequencies are much higher in alcoholics than in nonalcoholics (26.4% vs 9.6% for c2 and 27.8% vs 13.5% for C allele). Taken together, ADH3*2 and CYP2E1 c2/C alleles might independently contribute to the development of alcoholism in Mexican American men.     

Influence of CYP4F2, ApoE,and CYP2A6 gene polymorphisms on the variability of Warfarin dosage requirements and susceptibility to cardiovascular disease in Jordan

Cardiovascular diseases are among the leading causes of death worldwide. Many of those diseases require treatment with warfarin, an anticoagulant that has a large high inter and intra-variability in the required doses. The aim of this study is to find if there are any associations between rs2108622 of CYP4F2, rs7412 and rs405509 of ApoE, and rs1801272 of CYP2A6, and CVD and warfarin dose variability. The selected genes and their polymorphisms are involved in many GWAS associated with cardiovascular disease and variability in warfarin treatment. The study sample consisted of 212 Jordanian Cardiovascular patients and 213 healthy controls. DNA was extracted and the Mass ARRAY™ system was used to genotype four selected SNPs within three genes (CYP4F2, ApoE, and CYP2A6). Only one out of the four selected SNPs (ApoE rs7412 SNP) was found to be associated with the risk of cardiovascular disease. Also, this SNP showed significant differences in warfarin initial doses. CYP2A6 rs1801272 SNP was found to be associated with warfarin sensitivity during the initiation phase of therapy and with warfarin responsiveness and INR measurement during the stabilization phase of therapy. This study improves the current understanding of the high inter and intra-variabilities in response to warfarin, including the variety of dosing requirements and the susceptibility to cardiovascular disease in the Jordanian Arab population. Further study on a larger sample and in different ethnic groups could help in improving our understanding of warfarin''s pharmacogenetics and its application in personalized medicine.     

Association of CYP2C19*2 and *3 Genetic Variants with Essential Hypertension in Koreans

Purpose

The cytochrome P450 2C19 (CYP2C19) metabolizes arachidonic acid to produce epoxyicosanoid acids, which are involved in vascular tone and regulation of blood pressure. Recent findings suggest that CYP2C19 gene might be considered as a novel candidate gene for treatment of cardiovascular disease. The aim of the present study was to evaluate the association between two variants, CYP2C19^*2 (681G>A) and CYP2C19^*3 (636G>A) and the development of essential hypertension (EH) in Koreans.

Materials and Methods

We carried out an association study in a total of 1190 individuals (527 hypertensive subjects and 663 unrelated healthy controls). The CYP2C19 polymorphisms were genotyped using the SNaPShot™ assay.

Results

The distribution of alleles and genotypes of CYP2C19^*3 showed significant difference between hypertensive patients and normal controls (p=0.011 and p=0.013, respectively). Logistic regression analysis indicated that the CYP2C19^*3 (636A) allele carriers were significantly associated with EH [odds ratio, 0.691; 95% confidence interval (CI), 0.512-0.932, p=0.016], in comparison to wild type homozygotes (CYP2C19^*1/^*1). Neither genotype nor allele distribution of CYP2C19^*2 polymorphism showed significant differences between hypertensive and control groups (p>0.05).

Conclusion

Our present findings strengthen the evidence of an association between CYP2C19 gene polymorphism and EH prevalence. In particular, the CYP2C19^*3 defective allele may contribute to reduced risk for the development of EH.     

韩国人CYP450 1A1、CYP450 2E1和GSTM1、GSTT1、GSTP1基因座遗传多态性分析

目的 调查代谢相关的CYP4501A1、CYP4502E1和GSTM1、GSIT1、GSTP1基因座在韩国人群中的遗传多态性分布状况。方法 采用多重聚合酶链式反应、聚合酶链式反应-限制性片段长度多态性技术，分析300名韩国健康大学生的CYP1A1基因3′端限制性内切酶Msp Ⅰ位点、CYP2E1基因5′端转录调节区Pst Ⅰ位点和GSTM1、GSTT1缺失与存在、GSTP1基因第5外显子BsmA Ⅰ位点的基因型，计算基因型和基因频率。结果 CYP1A1基因型频率为ml／ml型39．7％、ml／m2型49．7％、m2／m2型10．7％，基因频率为ml 0．645、m2 0．355。CYP2E1基因型频率为cl／cl型66．7％、cl／c2型30％、c2／c2型3．3％，基因频率为C1 0．818、C2 0．182。GSTM1基因缺失型频率为53．3％。GSTT1基因缺失型频率为54．7％。GSTP1基因型频率为Ile／Ile型62％、Ile／Val型34．3％、VaL／Val型3．7％，基因频率为Ile 0．792、Val 0．208。基因分布符合Hardy-Weirtberg平衡定律。结论 韩国人CYP1A1、CYP2E1、GSTM1、GSTT1基因分布与我国人群较为相近，半数以上人缺乏GSTM1和GSTT1基因，纯合缺失型频率超过印度人的3倍。     

CYP2C19、CYP3A5基因多态性与心肌梗死的相关性研究

目的探讨CYP2C19、CYP3A5基因的多态性与心肌梗死发病风险的相关性。方法随机选取心肌梗死患者及健康对照各500例,采用荧光PCR法和Sanger测序分别检测其CYP2C19、CYP3A5基因的多态性,用Logistic回归分析其与心肌梗死的相关性,用Quanto软件评估统计学效能。结果CYP2C19基因rs4986893位点的AG、GG基因型和A等位基因的频率以及CYP3A5基因rs776746位点的AA、AG、GG基因型和G等位基因频率在两组之间的差异具有统计学意义(P<0.05),CYP2C19基因rs4244285、rs12248560位点的基因型和等位基因以及rs4986893位点的AA基因型的频率在两组之间差异无统计学意义(P>0.05)。在校正年龄、性别、体质指数后,Logistic回归分析显示CYP2C19基因rs4986893的AG基因型和A等位基因以及CYP3A5基因rs776746的GG基因型和G等位基因可能是心肌梗死发病的风险因素,而rs4986893的GG基因型以及rs776746的AA、AG基因型可能是心肌梗死的保护因素。依据样本量、样本结构和等位基因频率以及Quanto分析,本研究的结果具有理想的统计学效能(99%)。结论CYP2C19、CYP3A5基因的多态性可能增加心肌梗死的发病风险。