Polymorphic markers TCF7L2 rs12255372 and SLC30A8 rs13266634 confer susceptibility to type 2 diabetes in a Russian population

Abstract

Genes 7CF7L2 and SLC30A8, encoding transcription factor-4 and transmembrane zinc transporter-8, respectively, play an important role in the regulation of development, proliferation, and pancreatic beta cell function. In the present study we examined polymorphic markers of genes rs12255372 [NT_03359.12:g33557428G --> T] of 7CF7L2 gene and rs13266634 [NP_776250.2:p.R325W] of SLC30A8 in groups of Russians with type 2 diabetes (T2D) (n = 588) and healthy normoglycemic controles (n = 597). Significant association of allele T(rs12255372) and allele R (rs13266634) with a higher risk of T2D development has been found (OR = 1.37 and 1.22, respectively). Adjustment for the effect of potential nongenetic risk factors resulted in a further increase in the OR values, from 1.54 (P = 0.24) to 1.89 (P = 0.046) for homozygous carriers of the T allele and from 1.29 (P = 0.035) to 1.35 (P = 0.019) in the individuals homozygous for the R allele. The patients homozygous for predisposing allele T (rs12255372) or R (rs13266634) had significantly lower insulin concentrations in the blood 2 h after glucose tolerance test (GTT) as well as lower values of HOMA-beta, beta cell homeostasis indicator compared to the carriers of other genotypes. Thus, we have shown that the rs12255372 and rs13266634 markers are independent genetic T2D risk factors in a Russian population.