Differences in genotype and allele frequency distributions of polymorphic drug metabolizing enzymes CYP2C19 and CYP2D6 in mainland Chinese Mongolian, Hui and Han populations

Yin, Sheng-Ju; Ni, Yuhua; Wang, S.-M.; Wang, X.; Lou, Ya-Qing; Zhang, G.-L.

doi:10.1111/j.1365-2710.2011.01298.x

Cited by 31 publications

(17 citation statements)

References 46 publications

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“…Two hundred and eleven studies not fulfilling the eligibility criteria were further excluded. Finally, a total of 86 studies were included in this review. These included 25, 24, 20 and 17 studies on CYP2C9 , CYP2C19 , CYP2D6 and CYP3A5 , respectively.…”

Section: Resultsmentioning

confidence: 99%

CYP2C9, CYP2C19, CYP2D6 and CYP3A5 polymorphisms in South‐East and East Asian populations: A systematic review

2019

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Summary What is known and objective Genetic polymorphism is one of the most important factors responsible for interindividual and interethnic variability in drug response. Studies in major populations, ie, Caucasians, Asians, and Africans, have provided evidence of differences in the genotype frequencies of major drug‐metabolizing enzyme cytochrome P450 (CYP). This study aimed to review systematically, all relevant articles related to the genetic polymorphisms in CYP2C9, CYP2C19, CYP2D6 and CYP3A5 in South‐East and East Asian (SEEA) populations. Methods Articles that report genetic polymorphisms, genotype frequencies and allele frequencies in CYP2C9, CYP2C19, CYP2D6 and CYP3A5 were retrieved from the PubMed database. Results and discussions A total of 86 studies that fulfilled the eligibility criteria representing different ethnic populations of SEEA, ie, Burmese, Chinese, Japanese, Karen ethnic minority, Korean, Malaysian, Philippino, Singaporean, Taiwanese, Thai, Indonesian, and Vietnamese, were included in the analysis. In general, the genotype frequencies across SEEA populations are comparable. The CYP2C9*1/*1 (69.3%‐99.1%), *1/*3 (2.3%‐20.1%) and *3/*3 (0%‐2.2%) genotypes are reported in most SEEA populations. Six major CYP2C19 genotypes, ie, *1/*1 (6.25%‐88.07%), *1/*2 (21.5%‐86.46%), *1/*3 (0.8%‐15.8%), *2/*2 (3.4%‐14.5%), *2/*3 (0%‐7.3%) and *3/*3 (0%‐10.2%), are reported in most SEEA populations. Major CYP2D6 genotypes include *10/*10 (0%‐69.6%), *1/*1 (0%‐61.21%) and *1/*10 (0%‐62.0%). Major CYP3A5 genotypes are *3/*3 (2.0%‐71.4%), *1/*3 (16.0%‐57.1%) and *1/*1 (0%‐82.0%). Genotyping of abnormal genotypes of CYP2C9 (*1/*3), CYP2C19 (*1/*2, *1/*3), CYP3A5 (*1/*3) and CYP2D6 (*5/*10) associated with IM (Intermediate metabolizer) status, may be clinically beneficial in SEEA populations. Similarly, with CYP2C19 (*2/*2, *2/*3), CYP2D6 (*5/*5 ) linked to PM (Poor metabolizer), CYP2D6 (*10/*10, *1/*5 and to lesser extent *1/*4, *2/*5, *10/*41, *10/*49, *10/*14) and CYP3A5 (*1/*1) associated with EM (extensive metabolizer). What is new and conclusion Sufficient number of studies has provided comparable results in general. This review suggests that comparable genotype frequencies of CYP2C9, CYP2C19, CYP2D6 and CYP3A5 exist among the SEEA populations. It is noted that more research data are reported from East Asians compared with South‐East Asians. Concerned efforts are required to establish partnerships among SEEA countries that will ensure sufficient data from South‐East Asian countries which will assist in establishing the databases for SEEA populations.

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Section: Resultsmentioning

confidence: 99%

CYP2C9, CYP2C19, CYP2D6 and CYP3A5 polymorphisms in South‐East and East Asian populations: A systematic review

2019

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“…[13] found that the allele frequencies of CYP2C19*2 were respectively 29.7%, 32.4% and 18.2% in Han, Hui and Mongolian, the allele frequencies of CYP2C19*3 were respectively 7.9%, 10.2% and 11.2% in Han, Hui and Mongolian. Other literatures [14,15] reported that the allele frequencies of CYP2C19*2 were 11.1% for Western Africa, 14.0% for Western Europe and 16.3% for Northern Europe respectively, and the allele frequencies of CYP2C19*3 were 0% for Western Africa, 0.2% for Western Europe and 0.2% for Northern Europe respectively.…”

Section: Discussionmentioning

confidence: 99%

Association between genetic polymorphisms of cytochrome P450 2C19 and the risk of cerebral ischemic stroke in Chinese

Sun

Han

et al. 2014

BMC Med Genet

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BackgroundCytochrome P450 (CYP) 2C19 is a very important drug metabolizing enzyme. Although the single nucleotide polymorphisms (SNPs) of CYP2C19 G681A and G636A have been suggested that they may increase the incidence of cardiovascular events, the relationship between SNPs in CYP2C19 and cerebral ischemic stroke (CIS) are unclear. The aim of this study was to investigate the correlation between the distribution of G681A and G636A polymorphisms in CYP2C19 gene and the risk of CIS in Chinese.MethodsThe peripheral blood DNA was extracted from 299 patients with CIS and 295 healthy controls. The genotyping was conducted using the polymerase chain reaction-restriction fragment length polymorphism. The sampled sequencing was applied to verify the correctness of genotyping results. Both the genotype and allele distributions were compared in patients with CIS and healthy controls.ResultsThe frequencies of CYP2C19 681AA (11.7% vs. 2.7%; P = 0.000), 636AA (4.0% vs. 0.7%; P = 0.007), 636AG (7.0% vs. 2.2%; P = 0.038) genotype, CYP2C19 681A (30.9% vs. 20.8%; P = 0.000) and 636A (13.0% vs. 5.8%; P = 0.000) allele in the CIS group are significantly higher than those in the controls. The frequencies of CYP2C19 681AA (16.7% vs. 8.6%; P = 0.036), CYP2C19 636AA (7.0% vs. 2.2%; P = 0.038) genotype, CYP2C19 681A (36.4% vs. 27.6%; P = 0.023) and CYP2C19 636A (17.5% vs.10.3%; P = 0.010) allele in the recurrent stroke group are significantly higher than those in the first onset group. Multivariate logistic regression analysis of risk factors for cerebral ischemic stroke and recurrent stroke respectively suggests that the CYP2C19 681AA genotype may be an independent risk factor for CIS (OR = 6.179, 95% CI: 2.285 ~ 16.708; P = 0.000) and recurrent stroke (OR = 2.305, 95% CI: 1.121 ~ 4.743; P = 0.023).ConclusionsThe AA genotype and A allele of CYP2C19 G681A may be related to the occurrence and recurrence of cerebral ischemic stroke.

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“…Trials conducted in East Asia have reported the frequency of PM phenotype in the range 17–23% in healthy Asians, 9–28% in Chinese, and only 2–5% in healthy Caucasians. The biggest inter‐ethnic difference for the CYP2C19 PM phenotype is reported between Chinese Hui and Dai minorities (25% vs 9.3%, respectively) …”

Section: Ethnic Distribution Of Cyp2c19 Polymorphisms—is It Clinicallmentioning

confidence: 97%

“…The biggest inter-ethnic difference for the CYP2C19 PM phenotype is reported between Chinese Hui and Dai minorities (25% vs 9.3%, respectively). 58,59 Association of CYP2C19 alleles and risk of cardiovascular adverse events. An increasing number of studies conducted in Asian countries show that reduced function CYP2C19 alleles are associated with an increased risk of vascular events.…”

Section: Introductionmentioning

confidence: 99%

East Asian perspective on the interaction between proton pump inhibitors and clopidogrel

Zou

Goh

2017

J of Gastro and Hepatol

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Both proton pump inhibitors (PPIs) and clopidogrel are widely prescribed in the Asia-Pacific population. PPIs are the mainstay therapeutic agents for prophylaxis against aspirin gastropathy and for acid-related disorders including gastroesophageal reflux disease. They are also co-prescribed with oral anticoagulant agents and with dual-antiplatelet therapy for the treatment and prevention of gastrointestinal bleeding. Clopidogrel belongs to the drug class of thienopyridines and is currently the most widely prescribed oral anticoagulant agent either alone or in combination with aspirin. Platelet inhibition by clopidogrel is prone to significant inter-individual variability and is believed to be affected by several factors such as genetics and drug-drug interactions. Since it was first reported in 2009, the potential for drug-drug interactions between PPIs and clopidogrel has remained headline news, and its significance in clinical practice is the subject of an ongoing debate. For East Asian patients in particular, the clinical relevance of the interaction between PPIs and clopidogrel remains unclear because of conflicting data, as well as underrepresentation of East Asian subjects in landmark trials. Increased CYP2C19 genetic polymorphisms in individuals from Asia-Pacific countries only fuel the confusion. Recent studies in East Asian cohorts suggests that the potential of PPIs to attenuate the efficacy of clopidogrel could be minimized by the use of newer PPIs with weaker affinity for the CYP2C19 isoenzyme, namely, pantoprazole, dexlansoprazole, and rabeprazole. This review aims to help clinicians choose the most appropriate PPI for co-prescription with clopidogrel in patients from Asia-Pacific countries.

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Differences in genotype and allele frequency distributions of polymorphic drug metabolizing enzymes CYP2C19 and CYP2D6 in mainland Chinese Mongolian, Hui and Han populations

Abstract: This is first report of interethnic differences in frequencies of functional CYP2C19 and CYP2D6 genes among Chinese Mongolian, Hui and Han populations. These differences may be important in explaining reported inter-ethnic differences in disease prevalence and response to drugs.

Cited by 31 publications

References 46 publications

CYP2C9, CYP2C19, CYP2D6 and CYP3A5 polymorphisms in South‐East and East Asian populations: A systematic review

CYP2C9, CYP2C19, CYP2D6 and CYP3A5 polymorphisms in South‐East and East Asian populations: A systematic review

Association between genetic polymorphisms of cytochrome P450 2C19 and the risk of cerebral ischemic stroke in Chinese

East Asian perspective on the interaction between proton pump inhibitors and clopidogrel

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