The increase in diabetes was noted at the turn of the 21st century. Patients with type 2 diabetes (T2DM) make up the majority of patients. Diabetes is a multifactorial disease. It arises from adverse effects of environmental factors on the body of genetically susceptible peoples. According to modern concepts, T2DM is a polygenic disease. Each of the involved genes contributes to the risk of developing of this disease. In our study, the association between polymorphic genetic markers rs7756992, rs9465871, rs7754840, and rs10946398 in the CDKAL1 gene and rs1111875 in the HHEX/IDE locus and T2DM in the Russian population were studied. Four hundred forty patients with type 2 diabetes and 264 healthy individuals without any signs of the disease were examined. The comparative analysis of distribution of genotypes and allele frequencies points to an association between polymorphic genetic markers rs7756992, rs9465871, and rs10946398 in the CDKAL1 gene and this disease. For the other polymorphic genetic markers (rs7754840 in the CDKAL1 gene and rs1111875 in the HHEX/IDE locus), no statistically significant associations are found. On the basis of these data, we can conclude that the CDKAL1 gene is associated with development of T2DM. For the HHEX/IDE locus, such an association is absent.

To test FTO, KCNJ11, SLC30A8, and CDKN2B for association with type 2 diabetes mellitus (DM), the allele and genotype frequency distributions were established for several polymorphisms of the genes. A comparison of allele and genotype frequencies between DM patients and healthy subjects implicated CKNJ11, SLC30A8, and CDKN2B, but not FTO, in the disease. The genes that affect insulin production and secretion in pancreatic β cells proved to play a main role in type 2 DM in the Russian population.

To study the association with diabetes mellitus type 2 we performed anal- ysis of the distribution of frequencies of alleles and genotypes of polymorphic markers of FTO, KCNJ11, SIC30A8 and CDKN2B genes. The study included groups of T2DM patients and unrelated controls of Russian origin. Analysis of the distribution of frequencies of alleles and genotypes of the polymorphic markers of KCNJ11, SLC30A8 and CDKN2B genes showed the presence of association with T2DM in Russian population, while for the FTO gene was not found statistically significant associations with type 2 diabetes. We can conclude that in Russian population main role in the development of type 2 diabetes play genes, affecting the level of syn- thesis and secretion of the insulin in beta-cells of the pancreas.

To study the association with diabetes mellitus type 2 we performed analysis of the distribution of frequencies of alleles and genotypes two polymorphic markers of TCF7L2 gene. The study included groups of T2DM patients and unrelated controls of Russian origin. Analysis of the distribution of frequencies of alleles and genotypes of the polymorphic marker rs7903146 of TCF7L2 gene showed the presence of association with T2DM in Russian population, while for the marker rs12255372 was not found statistically significant associations with type 2 diabetes. We can conclude that in Russian population TCF7L2 gene is associated with development of T2DM.

On chromosome 6q22.3, a cluster of single-nucleotide polymorphisms located in intron 5 of the cyclin-dependent kinase 5 (CDK5) regulatory subunit-associated protein 1-like 1 (CDKAL1) gene were shown to confer susceptibility to type 2 diabetes in multiple ethnic groups. The diabetogenic role of CDKAL1 variants is suggested to consist in lower insulin secretion probably due to the insufficient inhibition of the CDK5 activity. In this study, we assessed the association of several SNPs of CDKAL1 with T2D in 772 Russian affected patients and 773 normoglycemic controls using a Taqman-based allelic discrimination assay. We showed association of the minor allele C of rs10946398 (Odds Ratio (OR) = 1.21, 95% CI = 1.04–1.4, P = 0.016), allele C of rs7754840 (OR = 1.18, 95% CI = 1.01–1.37, P = 0.038), and allele G of rs7756992 (OR = 1.21, 95% CI = 1.04–1.42, P = 0.017) with higher diabetes risk thereby replicating the predisposing role of CDKAL1 in etiology of T2D. These alleles contribute to three haplotypes (CCA, CGG, and CCG) related to higher diabetes risk (OR = 1.48, 2.12, and 1.95). Combinations of these haplotypes between each other form the group of high-risk haplogenotypes whose carriers had decreased HOMA-β compared to other CDKAL1 variants in both diabetic (38.6 ± 19.3 vs. 48.2 ± 21.2, P adjusted = 0.019–0.044) and non-diabetic (91.8 ± 42.1 vs. 108 ± 47.2, P adjusted = 0.0054–0.01) patients. The carriage of the risk haplogenotypes of CDKAL1 was associated with reduced response to non-sulfonylurea and sulfonylurea agonists of the pancreatic KATP channel. These data suggest that CDKAL1 is involved in the pathogenesis of T2D through impaired beta-cell function.

The KCNJ11 and ABCC8 genes encode the components of the pancreatic ATP-sensitive potassium (KATP) channel, which regulates insulin secretion by β-cells and hence could be involved in the pathogenesis of type 2 diabetes (T2D). The KCNJ11 E23K and ABCC8 exon 31 variants have been studied in 127 Russian T2D patients and 117 controls using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) approach. The KCNJ11 E23 variant and the ABCC8 exon 31 allele A were associated with higher risk of T2D [Odds ratio (OR) of 1.53 (P = 0.023) and 2.41 (P = 1.95 × 10−5)], respectively. Diabetic carriers of the ABCC8 G/G variant had reduced 2 h glucose compared to A/A + A/G (P = 0.031). The G/G genotype of ABCC8 was also significantly associated with increased both fasting and 2 h serum insulin in diabetic and non-diabetic patients. A HOMA-β value characterizing the β-cell homeostasis was higher in the non-diabetic carriers homozygous for G/G (98.0 ± 46.9) then for other genotypes (HOMA-β = 85.6 ± 45.5 for A/A + A/G, P = 0.0015). The KCNJ11 E23K and ABCC8 exon 31 variants contribute to susceptibility to T2D diabetes, glucose intolerance and altered insulin secretion in a Russian population.