Normative genetic profiles of RAAS pathway gene polymorphisms in North Indian and South Indian populations

Abstract

Population-based genetic association studies, popularly known as case-control studies, have continued to be the most preferred method for deciphering the genetic basis of various complex diseases, even in the post-human genome sequencing era. However, interpopulation differences in allele, genotype, and haplotype frequencies and linkage disequilibrium patterns lead to inconsistent results in candidate gene association studies. Therefore, for any meaningful disease association study, knowledge of the normative genetic background of the baseline population is a prerequisite. In addition, such genetic variation data also provide a ready-made menu of allele frequencies and linkage disequilibrium patterns of various polymorphisms in specific candidate genes in a particular population, which is a useful reference for further genetic association studies. Such genetic variation data are lacking for the Indian population, which represents about one-sixth of the world's population. In the present study we have reported the allele, genotype, and haplotype frequencies, Hardy-Weinberg equilibrium status, and linkage disequilibrium patterns of 12 polymorphisms in six candidate genes from the reninangiotensin-aldosterone system among Indians. Because of their different history of origin, the Indian population is broadly divided into two subpopulations: North Indians (Caucasian Europeans) and South Indians (Dravidians). Considering this well-documented difference in gene pools, we have presented a comparative account of the normative genetic data of North Indian and South Indian populations with at least four individuals of urban and suburban origin from each of the representative states of northern and southern India.