Association analysis of TNFRSF1B polymorphisms with type 2 diabetes and its related traits in North India

Abstract

Inflammation plays a crucial role in the pathogenesis of type 2 diabetes and various lines of evidences suggest an important contribution of type 2 receptor for TNFa (TNFR2), a mediator of inflammatory responses. Though genetic association of TNFRSF1B (encoding TNFR2) polymorphisms have been investigated in various studies, their involvement is not clear because of inconsistent findings. Because of high susceptibility of Indian population to type 2 diabetes and its complications, we evaluated the association of TNFRSF1B polymorphismsrs1061622 (M196R; exon6) and rs3397 (3 0 UTR) and (CA) n repeat (intron 4) in 1,852 subjects including 1,040 cases and 812 controls with type 2 diabetes and its associated peripheral neuropathy and hypertension in North Indians of Indo-European ethnicity. The allelic and genotypic distributions of these polymorphisms were comparable among healthy control vs. type 2 diabetes, peripheral neuropathy vs. non-neuropathy and hypertensive vs. normotensive groups. (CA) n polymorphism has been shown to be associated with diabetic neuropathy in Caucasians, however, this could not be replicated in our study (P = 0.27). None of the polymorphisms were found to influence the 14 anthropometric and biochemical traits related to type 2 diabetes studied here. Thus, we conclude that TNFRSF1B is not a major contributing factor to the genetic risk of type 2 diabetes, its associated peripheral neuropathy and hypertension and related metabolic traits in North Indians.

Polymorphisms in CaSR and CLDN14 Genes Associated with Increased Risk of Kidney Stone Disease in Patients from the Eastern Part of India

“…Recent evidence suggests that the genetic basis of several diseases in Indians might be different from that of Europeans [ 17 , 18 ], this scenario may be due to differences in the risk allele frequency and linkage disequilibrium pattern. Hence, candidate genes of a disease in other populations need to be evaluated for their role in the Indian population.…”

Replication and Relevance of Multiple Susceptibility Loci Discovered from Genome Wide Association Studies for Type 2 Diabetes in an Indian Population

“…Moreover, Indians develop T2D a decade earlier at a BMI which is much lower than Caucasians and this has been, attributed to their increased central obesity. This phenotype of increased tendency towards resistance of insulin effect is referred to as “Asian-Indian phenotype” [ 23 ]. Thus, understanding the contribution of the common genetic loci on T2D risk in Indian population comparatively to those originally identified by GWAS of European and American population is extremely important.…”

Genetic etiology of type 2 diabetes mellitus: a review

“…Although there are no specific studies on gene-environment interactions in Indian populations, the environmental factors like diet and lifestyle changes due to urbanization coupled with Asian Indian Phenotype of high insulin resistance and greater abdominal fat deposition are tangible reasons to expect gene-environment interactions to have had played a significant role in the manifestation of T2DM as well its fast increasing prevalence, especially given evidence of gene-environment interactions in the non-Indian populations discussed earlier (genes with dietary interaction such as TCF7L2, PPARG and IGF2BP2 which influence the glucose levels, abdominal fat and insulin secretion). In this background it is also pertinent that the above genetic variants were found significantly associated with T2DM in the Indian populations [40,41,138,139,141,142].…”

“…On the other hand, the CDK5 which was studied only among the North Indian Sikhs [139] did not show any association with T2DM. Further, some rare variants such as FOXA2 [140] and TNFRSF1B [141] were …”