Analysis of CYP2C19 Genetic Polymorphism in a Large Ethnic Hakka Population in Southern China

Abstract

BackgroundCytochrome P450 (CYP) 2C19 is an enzyme involved in the bioactivation of various important therapeutic drugs, from pro-drugs to an active inhibitor of platelet action. Variants in the CYP2C19 gene influence the pharmacokinetics and clinical response to antiplatelet drugs such as clopidogrel; however, there is no available data about the genetic variation of CYP2C19 in the Hakka population in China.Material/MethodsA total of 6686 unrelated participants (ages 17–98 years) of self-reported Hakka ancestry admitted at an inpatient department in a hospital in southern China were successfully genotyped by the gene chip platform.ResultsThe identified allele frequencies were CYP2C19*1 (64.33%), *2 (31.06%) and *3 (4.61%). The major prevalent genotype combinations were CYP2C19 *1/*1 (41.73%) and *1/*2 (39.65%). The distribution of CYP2C19 phenotypes was divided into extensive metabolizers (EM) (41.73%), intermediate metabolizers (IM) (45.21%), and poor metabolizers (PM) (13.06%). In the Hakka population, frequencies of the CYP2C19 *2 and *3 variants were observed to be close to those previously identified in Chinese and several other Asian populations.ConclusionsOur study is the first to report on CYP2C19 polymorphisms in the Hakka population, and may help to optimize pharmacotherapy effectiveness by providing personalized medicine to this ethnic group in the near future.

Genetic polymorphism of the CYP2C19 gene in the Foshan area of Guangdong Province

“…The CYP2C19*2 allele frequency in the subjects of our study was higher than that reported for Caucasians. Interestingly, the CYP2C19*2 allele frequency in our group (30.46%) was closer to those of Hakka (31.06%) and Chinese-Dai (30%) populations [18][19]. As shown in Table 2, the CYP2C19*2 allele frequency in our group was closer to that reported for other Asian populations.…”

“…Caucasians (0.0-0.3%) [25][26][27][28][29], Africans (0.0-2.0%) [30][31][32], Asians (1.0-11.1%) [18][19][20][21][22][23][24]. The CYP2C19*3 allele frequency was reported to be 5.65% in the Foshan population, which is consistent with those in other Chinese populations [19][20][21].…”

“…The CYP2C19*1 allele (wild-type) frequency in the Foshan population was lower than that in Caucasian populations and Asian populations [25][26][27][28][29][30][31][32]. According to previous studies, the highest CYP2C9*2 allele frequency was found in Asians (21.0-49.39%) [18][19][20][21][22][23][24]; however, the lowest frequency was found in Caucasians (2.9-14%) [25][26][27][28][29]. The CYP2C19*2 allele frequency in the subjects of our study was higher than that reported for Caucasians.…”

Association Between CYP2C19 Polymorphisms and Esophageal Squamous Cell Carcinoma Risk in Asian Populations: A Systematic Review and Meta-analysis

“…The mechanism of CYP2C19*2 mutation is a 681 substitution of guanine to adenine (G > A) in the exon 5, which lead to a 40 base pair fragment containing a Smal restriction endonuclease site to be lost in the initial segment of exon 5 during transcription, causing an inactive enzyme. The CYP2C19*3 polymorphism is a 636 substitution of guanine to adenine (G > A) in the exon 4, causing the codon of tryptophan changing to a stop codon, which lead to a premature termination of protein synthesis and a lack of connective zone of the substrate and the hemochrome [10]. According to metabolic capacity, CYP2C19 can be divided into three phenotypes: extensive metabolizers (EMs), intermediate metabolizers (IMs), and poor metabolizers (PMs).…”

Development of a Korean‐specific virtual population for physiologically based pharmacokinetic modelling and simulation

“…For instance, the cytochrome P450 (CYP) 2D6*1 frequency is significantly higher in Japanese than in Koreans and Chinese, whereas the frequency of CYP2D6*10, a loss‐of‐function allele, in Koreans and Japanese is significantly lower than that in Chinese (Lee et al, ; Sohn et al, ). Additionally, CYP2C19*3, a decreased or no function allele, is relatively less frequently found in Chinese than in Koreans and Japanese, whereas the frequency of CYP2C19*17, an increased function allele, was relatively higher in Chinese than in Koreans and Japanese (Kim, Song, Kim, & Park, ; Sohn et al, ; Zhong et al, ). These genomic differences in DMEs could have contributed to distinct PK profiles between Koreans, Japanese and Chinese even though they are geographically close.…”