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. 2014 Oct 2:1:14014.
doi: 10.1038/hgv.2014.14. eCollection 2014.

NAT2 genetic variations among South Indian populations

Saikrishna Lakkakula  1 , Ram Mohan Pathapati  2 , Gyaneshwer Chaubey  3 , Arasambattu Kannan Munirajan  4 , Bhaskar Vks Lakkakula  5 , Rajasekhar Maram  1
Affiliations

NAT2 genetic variations among South Indian populations

Saikrishna Lakkakula et al. Hum Genome Var. .

Abstract

The N-acetyltransferases (NATs) are xenobiotic-metabolizing enzymes involved in the metabolism of drugs, environmental toxins and the aromatic amine carcinogens present in cigarette smoke. Genetic variations in NAT2 have long been recognized as the cause of variable enzymatic activity or stability, leading to slow or rapid acetylation. In the present study, we genotyped three single-nucleotide polymorphisms (SNPs) from the NAT2 gene (rs1799929, rs1799930 and rs1799931), using TaqMan allelic discrimination, among 212 individuals from six major South Indian populations and compared the results with other available Indian and worldwide data. All three of the markers followed Hardy-Weinberg equilibrium and were highly polymorphic in the studied populations. The constructed haplotypes showed a high level of heterozygosity. All of the populations in the present study commonly shared only four haplotypes out of the eight possible three-site haplotypes. The haplotypes exhibited fairly high frequencies across multiple populations, where three haplotypes were shared by all six populations with a cumulative frequency ranging from 88.2% (Madiga) to 97.0% (Balija). We also observed a tribal-specific haplotype. A strong linkage disequilibrium (LD) between rs1799929 and rs1799930 was consistent in all of the studied populations, with the exception of the Madiga. A comparison of the genomic regions 20-kb up- and downstream of rs1799930 in a large number of worldwide samples showed a strong LD of this SNP with another NAT2 SNP, rs1112005, among the majority of the populations. Moreover, our lifestyle test (hunter-gatherer versus agriculturist) in comparison with the NAT2 variant suggested that two of the studied populations (Balija and Madiga) have likely shifted their diet more recently.

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Figures

Figure 1
Figure 1
The inferred NAT2 haplotype frequencies in the different Indian populations. The haplotypes are coded according to the site order in Table 2.
Figure 2
Figure 2
The pairwise linkage disequilibrium between the SNP markers of the NAT2 gene in the different Indian populations. The color coding represents the D'/LOD values, and the values in the cells are the r2 multiplied by 100. (a) Mala; (b) Madiga; (c) Muslim; (d) Balija; (e) Sugali; (f) Reddy.
Figure 3
Figure 3
The NAT2 rapid and slow acetylator phenotypes in the different Indian populations.
See this image and copyright information in PMC

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