<i>NAT2</i> Sequence Polymorphisms and Acetylation ProFiles in Indians

Abstract

BACKGROUND: NAT2, a broad-spectrum drug-metabolizing gene, is of high pharmacogenetic interest. Based on seven different mutations in the NAT2 gene, an individual can either be categorized as a slow or fast acetylator. MATERIALS & METHODS: In order to characterize acetylation profiles of Indians, where data are poorly available, we sequenced the 873 bp NAT2 coding region in 250 Indians, covering the whole of India including three tribes. RESULTS: Altogether, 35 NAT2 alleles forming two acetylator phenotypes (distributed almost in equal proportion in India) were found; while the alleles determining slow acetylators were highly differentiated, the fast acetylator alleles were less in number but highly frequent. CONCLUSION: Interestingly, distribution of two different acetylation phenotypes correlated well with historical dietary pattern in India. The neighbor-joining phylogenetic tree based on NAT2 gene polymorphisms in worldwide humans revealed genetic affinities among populations with similar acetylation phenotypes, which also placed Indians and Africans together in a single cluster.