Abstract
BACKGROUND: Type 2 diabetes mellitus is a multi-factorial disease in which both genetic and non-genetic factors interact in order to precipitate the diabetic phenotype. Among various predisposing genetic loci, a pentanucleotide (CTTTA) Del/Ins variant in the 3'-UTR of the LEPR gene is associated with type 2 diabetes and its related traits. This study was done to explicate for the first time the association of this Del/Ins polymorphism of LEPR gene in type 2 diabetes patients belonging to the ethnic population of Kashmir valley. METHODS: 670 unrelated subjects comprising of 320 type 2 diabetes patients and 350 healthy controls were included in the study. Genotyping of the untranslated region of LEPR gene encompassing this Del/Ins variant was done by PCR-RFLP technique and results were validated by direct sequencing. RESULTS: Genotype frequencies for both type 2 diabetes cases and healthy controls were consistent with Hardy-Weinberg equilibrium (χ(2) = 3.09 and 2.37, P = NS). The Del/Del genotype was predominantly found in cases than controls (P = 0.003, OR: 0.62, CI: 0.45-0.85). Carriers of Ins/Ins genotype were relatively protected against the risk factors (P = 0.0004, OR: 0.31, 95% CI: 0.15-0.61). A positive association was observed between the Del allele and the risk factors of type 2 diabetes. CONCLUSION: The results elucidate that the CTTTA Del allele is a genotypic risk factor of type 2 diabetes in the Kashmiri population.