CYP2C19 and PON1 Polymorphisms Regulating clopidogrel Bioactivation in Chinese, Malay and Indian Subjects

• DOI: 10.2217/pgs.12.24
• Publication Date: 2012-03-30T13:31:25Z
• Authors: Mark Y Chan; Karen Tan; Huay-Cheem Tan; Pei-Tee Huan; Bei Li; Qian-Hui Phua; Hong-Kai Lee; Chi-Hang Lee; Adrian Low; Richard C Becker; Wen-Chong Ong; Mark A Richards; Agus Salim; E-Shyong Tai; Evelyn Koay
• Keywords: Male; China; Ticlopidine; Genotype; Platelet Aggregation; India; Polymorphism, Single Nucleotide; 618; 03 medical and health sciences; 0302 clinical medicine; Asian People; Gene Frequency; 617; Humans; CYP2C19; PON1; pharmacogenetics; Aged; clopidogrel; Asian; Aryldialkylphosphatase; Malaysia; Middle Aged; Clopidogrel; Cytochrome P-450 CYP2C19; Multivariate Analysis; Female; Aryl Hydrocarbon Hydroxylases; metabolism; Platelet Aggregation Inhibitors

AIM, MATERIALS & METHODS: We investigated the functional significance of CYP2C19*2, *3, *17 and PON1 Q192R SNPs in 89 consecutive Asian patients on clopidogrel treatment and the prevalence of functionally significant polymorphisms among 300 Chinese, Malays and Asian Indians.Both CYP2C19 loss-of-function alleles (*2 or *3) were associated with higher platelet reactivity while the CYP2C19 gain-of-function allele (*17) had lower platelet reactivity. For PON1, the median PRI was not significantly different between the QQ, QR and RR groups. The allele frequencies of CYP2C19*2, CYP2C19*3 and CYP2C19*17 were 0.280, 0.065 and 0.010 (rare) for Chinese, 0.310, 0.050 and 0.025 for Malays, and 0.375, 0.010 (rare) and 0.165 for Indians, respectively.Our data suggest that genotyping studies to investigate clopidogrel response should include CYP2C19*2 and *3 but not *17 polymorphisms in Chinese, and CYP2C19*2 and *17 polymorphisms but not *3 in Indians. All three polymorphisms should preferably be genotyped in Malays.