A case-control analysis of common variants in GIP with type 2 diabetes and related biochemical parameters in a South Indian population

Abstract

BackgroundGlucose-dependent insulinotropic polypeptide (GIP) is one of the incretins, which plays a crucial role in the secretion of insulin upon food stimulus and in the regulation of postprandial glucose level. It also exerts an effect on the synthesis and secretion of lipoprotein lipase, from adipocytes, important for lipid metabolism. The aim of our study was to do a case-control association analysis of common variants in GIP in association with type 2 diabetes and related biochemical parameters.MethodA total of 2000 subjects which includes 1000 (584M/416F) cases with type 2 diabetes and 1000 (470M/530F) normoglycemic control subjects belonging to Dravidian ethnicity from South India were recruited to assess the effect of single nucleotide polymorphisms (SNPs) in GIP (rs2291725, rs2291726, rs937301) on type 2 diabetes in a case-control manner. The SNPs were genotyped by using tetra primer amplification refractory mutation system-PCR (ARMS PCR). For statistical analysis, our study population was divided into sub-groups based on gender (male and female). Association analysis was carried out using chi-squared test and the comparison of biochemical parameters among the three genotypes were performed using analysis of covariance (ANCOVA).ResultInitial analysis revealed that, out of the total three SNPs selected for the present study, two SNPs namely rs2291726 and rs937301 were in complete linkage disequilibrium (LD) with each other. Therefore, only two SNPs, rs2291725 and rs2291726, were genotyped for the association studies. No significant difference in the allele frequency and genotype distribution of any of the SNPs in GIP were observed between cases and controls (P > 0.05). Analysis of biochemical parameters among the three genotypes showed a significant association of total cholesterol (P = 0.042) and low density lipoprotein (LDL) with the G allele of the SNP rs2291726 in GIP (P = 0.004), but this was observed only in the case of female subjects. However this association does not remain significant after correction for multiple testing by Bonferroni's inequality method.ConclusionNo statistically significant association was observed between any of the SNPs analysed and type 2 diabetes in our population. But the analysis of biochemical parameters indicates that the G allele in rs2291726 may be a putative risk allele for increased LDL cholesterol and further studies in other population needs to be carried out for ascertaining its role in cholesterol metabolism and subsequent cardiovascular risk.

Association analysis of common variants in FOXO3 with type 2 diabetes in a South Indian Dravidian population

“…Case and control samples used in this work were from Amrita Diabetes Awareness and Welfare Study and have been described elsewhere (Nair et al, 2010;Sugunan et al, 2010). Broadly, Indians belong to four major language families, Austro Asiatic (AA), Indo-European (IE), Tibeto-Burman (TB) and Dravidians (DR) (Indian Genome Variation, 2008).…”

Association analysis of 31 common polymorphisms with type 2 diabetes and its related traits in Indian sib pairs

“…In India most genetic studies of type 2 diabetes published to date have used hospital-based case–control designs for either establishing candidate genes in the metabolic pathways of interest [ 8 , 9 ] or validating GWAS findings [ 10 – 13 ]. Further, the studies on quantitative traits of type 2 diabetes in India are few [ 14 , 15 ] and have investigated a limited number of SNPs.…”

Common variants of GIP are associated with visceral fat accumulation in Japanese adults

“…To treat obesity by inhibiting GIP signaling, it is necessary to collect further evidence of the involvement of GIP and GIPR in the etiology of obesity. SNPs in or near GIP are associated with blood clinical parameters and plasma levels of GIP, but not with obesity traits (4,5,29). Although recent advances in GWASs have identified multiple genes, including GIPR, that are associated with human obesity (7), the genetic architecture underlying depot-specific adiposity remains unclear.…”