Pharmacogenetics of common SNP affecting drug metabolizing enzymes: comparison of allele frequencies between European and Malaysian/Singaporean.

Abstract

Compared to Europe, data on genetic variation in genes transcribing drug metabolizing enzymes among Asian is limited due to ethnic diversity. Here we compare frequencies for clinically relevant single nucleotide polymorphism (SNP) commonly observed in drug metabolizing enzymes between European and Malaysian/Singaporean. Minor allele frequencies (MAF) for the indicated SNPs for European, South Asian and East Asian populations were obtained from the NCBI website (https://www.ncbi.nlm.nih.gov/snp). The SNP prevalence among Malaysian/Singaporean was characterized from gene association studies. Generally, some SNPs in CYP2D6 and CYP2C19 do not show good agreement between the two populations as to the MAF value obtained. CYP2D6*4 tends to be more common among European, whereas CYP2D6*10 is more common in Malays and Chinese among Singaporean. Regardless of different phenotype, MAF of CYP2D6*4 for Indians is similar to that seen by the European. Singaporeans show smaller MAF for CYP2C19*17 but higher CYP2C19*2 frequencies as opposed to European ones. Following growing attention to the contribution of CYP3A4/5, N-acetyltransferases (NAT2), thiopurine methyltransferase (TPMT) and uridine diphosphate glucuronosyltransferases (UGT)2B7 in predicting drug response across Europe, there are limited pharmacogenetics (PGx) studies examining the gene-drug interaction among Malaysian/Singaporean. To better understand the heterogeneity of the drug response, PGx studies for the abovementioned enzymes between ethnics in Malaysian/Singaporean should be identified.