Single nucleotide polymorphisms of the ALDH2 gene in six Indian populations

Abstract

Background: Aldehyde dehydrogenase-2 (ALDH2) degrades acetaldehyde metabolized from ethanol. Its encoding gene ALDH2 has a functional polymorphism, ALDH2 Glu487Lys associated with low enzyme activity. Aim: Since Glu487Lys of this locus is fixed for the functional subunit in all non-East Asian populations, this polymorphism was examined along with G-357A promoter (SacI) and four other intronic loci to identify informative markers to study the role of this gene in Indian populations. Subjects and methods: A total of 397 males belonging to six ethnic populations, from four linguistic groups of India were included in the present study. No test was performed to detect the phenotype of alcoholism. Genotype of ALDH2^∗E487K and G-357A promoter site along with four non-coding single nucleotide polymorphisms (SNPs) in the upstream of this polymorphism were determined by PCR and sequencing. Results: All of the subjects were found to have the common homozygous genotype (ALDH2^∗1/ALDH2^∗1) for the E487K site. Allele frequencies of non-coding SNPs varied among populations but genetic variance (F_st) indicated little variation among populations. Four major SNP-defined haplotypes accounted for almost all chromosomes in all populations. The ancestral haplotype was found in high frequency in all populations and linkage disequilibrium was strong and highly significant between all sites (p < 0.05). Conclusion: The small number of haplotypes in this region is suggesting the strong linkage disequilibrium across the region and confirms the global long-range linkage disequilibrium around the ALDH2 locus. This study provides a baseline for future research into the role of the ALDH2 locus in alcoholism in Indian populations.