药物基因组学和药物蛋白质组学杂志

抽象的

Cross-Ethnic Distribution of Clinically Relevant Cyp2c19 Genotypes and Haplotypes

Narazah Mohd Yusoff*, Mohamed Saleem, Devaki Nagaya, Badrul Hisham Yahaya, Rasmaizatul Akma Rosdi, Nurfadhlina Moosa, Rusli Ismail and Tan Soo Choon

Study background: Knowledge of the drug metabolism phenotype of a patient is critically important to making an informed choice about therapeutic drug prescription. The objective of this study was to determine the prevalence of common clinically relevant variants of the CYP2C19 gene in Malaysian ethnic groups and in other Asian and Middle Eastern populations, and to predict their metabolic phenotypes.

Methods: A total of 1103 subjects from six ancestral origins were genotyped for 16 single nucleotide polymorphic (SNP) markers on the CYP2C19 gene to comprehensively understand their allelic distributions. The expectationmaximisation algorithm was used to analyse the genotype data to estimate the maximum likelihood haplotypes in each sample group and to predict the clinical phenogroups.

Results: Of the 16 SNP loci genotyped in the six subpopulations studied, only four SNP markers (rs17885098, rs4986893, rs4244285 and rs3758581) showed polymorphism (minor allele frequency >1.0%). Nearly half of the Indians (55%) and Chinese (48.8%) had at least one copy of the loss-of-function allele. The incidence was relatively lower in Malays (39.3%), Orang Asli (27.3%), Javanese (23.8%) and Saudis (28%).

Conclusion: These ethnic groups pose a significant risk of drug sensitivity should they are prescribed regular doses of CYP2C19 substrate.