Genetic polymorphism of Pro12Ala in type 2 diabetes mellitus: Role in inflammation linked to Insulin resistance.

Abstract

Peroxisome Proliferator-Activated Receptor gamma 2 (PPARγ2) belongs to nuclear receptor superfamily and plays a role in adipocyte differentiation and inflammation. Evidences suggest that inflammatory processes hold key to insulin resistance and PPARγ2 has also been implicated. PPARγ2 exhibits gene polymorphism. The Ala allele of Pro12Ala polymorphism (rs1801282) is associated with a reduced risk for insulin resistance. We attempted the study in overweight and obese males to generate evidences linking insulin resistance, inflammatory mediators, and gene polymorphism of PPARγ2 in overweight and obese males. The conventional biochemical parameters were estimated using established methods. Adiponectin and Haptoglobin were quantitated by ELISA, whereas Ferritin and hs-CRP were by chemi-luminescence. Indices of insulin sensitivity /Insulin resistance were computed based on established formulae. Gene analysis was based on PCR and RFLP. Appropriate statistical analysis was enabled to project gene polymorphism.The heterozygous variant (CG) was around 8 and 38 percent respectively in overweight and obese males. The G Allele was 3.89% and 18.82%. The wild type and heterozygous variant of PPARγ2 depicted significance with haptoglobin, whereas adiponectin showed significance in the wild type. Chi-square test was performed to assess the relation between polymorphic genotypes and ferritin emerged significant. Indices of insulin resistance showed different characteristics with wild type and heterozygous variant ofPPARγ2 gene polymorphism. The inflammatory mediators (hs-CRP, Ferritin, Haptoglobin and adiponectin) exhibited variegated characteristics with the wild type and heterozygous variant of PPARγ2, thus pointing to the nexus among insulin resistance, inflammation, and adipocyte differentiation.