Variations and Their Pharmacogenetic Implications Among Diverse South Asian Populations.

INTRODUCTION

Allelic frequency distribution of drug metabolizing enzyme genes among populations is important to identify risk groups for adverse drug reaction and to select representative populations for clinical trials. Although India emerged as an important hub for clinical trials, information about the pharmacogenetic diversity for this region is still lacking. Here, we investigated genetic diversity of cytochrome-P450-2C9 () gene which metabolizes wide range of drugs and is highly expressed in the human liver.

METHODS

In total, 1278 individuals from 36 diverse Indian populations, 210 individuals from in-house data-repository and 489 other South Asian samples from the 1000 Genomes Project were selected. Variants observed in gene were subjected to various statistical analyses.

RESULTS

High frequency of (13%) and (1%) was observed among South Asians, compared to 21 populations living outside the Indian subcontinent. The allelic/genotypic frequency does not correlate with geographical location or linguistic affiliation, except populations speaking Tibeto-Burmans language, who have lower frequency of and . Since, South Asians practice strict endogamy, presence of unique mutation and high frequency of homozygous genotypes not surprising. has been associated with therapeutic response.The effect of is more pronounced compared to heterozygous and wild type homozygous genotypes as evident in many studies. As South Asians have high frequency, it would be interesting to explore potential of as a marker for personalized therapy. Our study revealed several rare functional variants, which form eight novel and rare haplotypes of (*63-*70). Of which, and haplotypes are South Asian-specific.

CONCLUSION

Overall, we find high genetic heterogeneity within South Asians and identified South Asian-specific putative functional haplotypes. High frequency of and was observed in South Asian populations. Taken together, current study greatly enriches the knowledge of naturally occurring variants and its diversity in South Asia, which are relevant to further -related functional research and for personalized medicine.