Abstract
INPPL1 gene encodes a lipid phosphatase Src homology 2-containing 5′-inositol phosphatase 2 (SHIP2) which is involved in the negative regulation of insulin signaling. In the light of several association studies of INPPL1 gene polymorphisms with T2DM, and the absence of association studies from India, present study was conducted to assess the association of two SNPs of INPPL1 gene with T2DM risk in North Indian population. Two single nucleotide polymorphism (SNPs) (+1893CC/AA and + 2945AA/GG) in INPPL1 gene were genotyped in total of 270 subjects with PCR-RFLP genotyping method. It was observed that, out of the two SNPs, only +1893CC/AA was found to be significantly associated with T2DM and frequency of A allele (C vs A, p = 0.002) has been found to be significantly higher in T2DM cases. Strong linkage disequilibrium was observed between two SNPs as assessed through D′ and r 2 (D′ = 0.984, r 2 = 0.009) and AG haplotype (OR = 3.59, 95% CI (1.59–9.80), p = 0.0015) was associated with increased risk of T2DM while CG haplotype (OR = 0.54, 95% CI (0.33–0.88) p = 0.012) significantly decreases the risk of developing T2DM. Regression analysis showed that SNP +1893CC/AA is associated with T2DM risk when adjusted for clinical/demographic variables. Results showed that INPPL1 gene polymorphism +1893CC/AA may increase susceptibility to T2DM and ‘A' allele might be serving as a risk factor in development of T2DM in Indian population. • Many factors responsible for pathogenesis of T2DM are influenced by genetic factors such as gene polymorphisms. Impairment in the function of genes related to insulin action is a major cause of insulin resistance that leads to development of T2DM. • Current study conducted on variants in INPPL1 gene so that the results might enhance the knowledge related to INPPL1 gene contribution to T2DM risk. • A allele of SNP +1893 CC/AA was found to be more frequent in T2DM subjects as compared to control subjects, therefore A allele might be a predisposing factor in development of T2DM. • Both SNPs (+1893 CC/AA and + 2945AA/GG) are in strong linkage disequilibrium and haplotype analysis revealed that individuals with AG might be on greater risk for T2DM while CG haplotype individuals might be at lower T2DM risk in North Indian population. • No significant association was observed between polymorphism +2945 AA/GG and T2DM risk.
Published Version
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