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

Aims: Markers rs12255372 (G/T) of the transcription factor 7-like 2 (TCF7L2) and rs13266634 (R325W) of the solute carrier family 30 (zinc transporter) member 8 (SLC30A8) showed association with type 2 diabetes (T2D) in multiple ethnic groups. In this study, we evaluated whether these markers confer susceptibility to T2D in a Russian population. Methods: Using a direct DNA sequencing, we genotyped these markers in 588 unrelated Russian T2D patients and 597 normoglycemic non-diabetic controls at age 50 and older. Association between these markers and patients' clinical and metabolic traits was assessed by the ANCOVA analysis, with adjustment for possible confounding risk factors. Results: The allele T of rs12255372 and allele R of rs13266634 showed significant association with a higher diabetes risk (Odds Ratio (OR) = 1.37 and 1.22, respectively). Adjustment for confounding risk factors strengthened the association increasing OR from 1.54 (p = 0.24) up to 1.89 (p = 0.046) in homozygotes T/T and from 1.29 (p = 0.035) up to 1.35 (p = 0.019) in homozygotes R/R. Compared to other genotypes, homozygous carriers of the risk variants of TCF7L2 and SLC30A8 (both diabetic and nondiabetic) had significantly lower levels of 2 h insulin and decreased values of the homeostasis model assessment of beta-cell function (HOMA-beta). Conclusions: TCF7L2 rs12255372 and SLC30A8 rs13266634 modulate risk of T2D in a Russian population through impaired function of beta-cells. (C) 2009 Diabetes India. Published by Elsevier Ltd. All rights reserved.