Analyses of frequency profiles of markers on disease or drug-response related genes in diverse populations are important for the dissection of common diseases. We report the results of analyses of data on 405 SNPs from 75 such genes and a 5.2 Mb chromosome, 22 genomic region in 1871 individuals from diverse 55 endogamous Indian populations. These include 32 large (>10 million individuals) and 23 isolated populations, representing a large fraction of the people of India. We observe high levels of genetic divergence between groups of populations that cluster largely on the basis of ethnicity and language. Indian populations not only overlap with the diversity of HapMap populations, but also contain population groups that are genetically distinct. These data and results are useful for addressing stratification and study design issues in complex traits especially for heterogeneous populations.

It has been speculated that IL-1 genes play a crucial role in the genetic predisposition to duodenal ulcer upon H. pylori infection by modulating the host immune response. In the present study, 310 individuals from Eastern India were subjected to a case-control study to determine the IL1B and IL1RN risk genotypes to H. pylori mediated duodenal ulcer. An analysis of genotype frequency revealed a significantly higher frequency of IL1B -511TT (NT_022135.14:g.2302610C>T), OR=4.22 (95% CI=1.8-9.4) and -31CC (NT_022135.14:g.2302130C>T), OR=2.16 (95% CI 1.12-4.15) genotypes in H. pylori-infected individuals with duodenal ulcer compared to infected individuals with normal mucosa. Moreover, the T/C haplotype of IL1B -511 and IL1B -31 loci was present in a significantly higher frequency in H. pylori-infected duodenal ulcer patients than in infected controls (OR=2.47, CI=1.27-4.8). Quantitative analysis of the mucosal IL1B mRNA revealed that among H. pylori-infected individuals, carriers of the -31CC genotype had significantly lower IL1B transcript levels than carriers of the CT (P<0.001) and TT (P<0.001) genotypes, independently of disease status. An IL1B promoter activity assay showed that the promoter with -31T had a 10-fold increase in activity compared to the one with -31C. The IL1B promoter bearing the different combinations of both polymorphic loci showed an interaction between the -511 and -31 loci. Our results show that H. pylori-infected individuals with the -31CC genotype secrete less IL1B and are susceptible to duodenal ulcers. They also suggest that the allelic interaction between the -511 and -31 polymorphic sites determines the overall strength of the IL1B promoter.

The genetic epidemiology of GS is variable across ethnic groups and the epistatic interactions among UGT1A1 promoter variants modulate bilirubin glucuronidation.

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