AB121. NAT2 sequence polymorphisms and acetylation profiles in Indians

Abstract: Evolutionary study of genes and genomes are helpful in decoding the role played by various evolutionary forces including footprints of natural selection. These forces change the architecture of genes for their best adaption in a particular environment. Inter-individual variations in drug response are responsible for adverse drug reactions, therapeutic drug failure and susceptibility to other diseases, thus understanding the genetic basis of drug metabolization serves as a key to inter-individual drug responses. To this respect, human N-acetyltransferase 2 (NAT2) is a drug metabolizing gene that helps in the metabolism of wide variety of drugs used for treating different diseases. The effective metabolization of exogenous chemicals by NAT2 gene classifies individuals into two acetylator phenotypes; fast (rapid) acetylator and slow acetylator. In order to determine which of the two acetylation phenotypes are prevalent in Indian population, we sequenced NAT2 873 bp coding region in 250 Indian populations collected from six geographical zones (North India, West India, South India, Central India, East India and North East India) and three tribal populations residing in Odisha (East India). On the basis of seven common NAT2 SNPs found in worldwide population, the individuals can be categorized as fast acetylator and slow acetylator. Thus, evolutionary analysis of drug metabolizing gene helps in understanding the metabolism of different therapeutic drugs and exogenous chemicals present in diet. Furthermore, the polymorphisms present in NAT2 gene will be used to understand how the variability of gene has evolved and how it affects the drug response mechanism in Indian populations.

Keywords: Indian population; drug metabolizing gene; polymorphisms; N-acetyltransferase 2 gene (NAT2 gene); evolutionary analysis