Association of polymorphisms of genes TCF7L2, FABP2, KCNQ1, ADIPOQ with the prognosis of the development of type 2 diabetes mellitus

Abstract

Aim. To study the possibility of using polymorphisms of genes TCF7L2, FABP2, KCNQ1, ADIPOQ as markers for predicting the development of type 2 diabetes mellitus (T2D) in the population of Novosibirsk. Materials and methods. On the basis of prospective observation of a representative population sample of residents of Novosibirsk (HAPIEE), 2 groups were formed according to the “case-control” principle (case – people who had diabetes mellitus 2 over 10 years of observation, and control – people who did not developed disorders of carbohydrate metabolism). T2D group (n=443, mean age 56.2±6.7 years, men – 29.6%, women – 70.4%), control group (n=532, mean age 56.1±7.1 years, men – 32.7%, women – 67.3%). DNA was isolated by phenol-chloroform extraction. Genotyping was performed by the method of polymerase chain reaction with subsequent analysis of restriction fragment length polymorphism, polymerase chain reaction in real time. Statistical processing was carried out using the SPSS 16.0 software package. Results and discussion. No significant effect of rs1799883 of the FABP2 gene, rs2237892 of the KCNQ1 gene, and rs6773957 of the ADIPOQ gene on the risk of developing T2D was found. Genotypes TT and TC rs7903146 of the TCF7L2 gene are genotypes for the risk of developing T2D (relative risk – RR 3.90, 95% confidence interval – CI 2.31–6.61, p<0.001; RR 1.86, 95% CI 1.42–2.43, p<0.001, respectively). The CC genotype rs7903146 of the TCF7L2 gene is associated with a protective effect against T2D (RR 0.37, 95% CI 0.29–0.49, p<0.001). When the TCF7L2 gene is included in the model for assessing the risk of developing T2D rs7903146, it retains its significance in both men and women. Conclusion. The rs7903146 polymorphism of the TCF7L2 gene confirmed its association with the prognosis of the development of T2D, which indicates the possibility of considering it as a candidate for inclusion in a diabetes risk meter. Variants of risk meters have been developed to assess the prognosis of the development of diabetes mellitus 2 in men and women aged 45–69 years during 10 years of followup. The association with the prognosis of the development of T2D polymorphisms rs1799883 of the FABP2 gene, rs2237892 of the KCNQ1 gene and rs6773957 of the ADIPOQ gene was not found.