[Association of the polymorphisms of the FTO, KCNJ11, SLC30A8 and CDKN2B genes with type 2 diabetes].

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.

The carriage of risk variants of CDKAL1 impairs beta-cell function in both diabetic and non-diabetic patients and reduces response to non-sulfonylurea and sulfonylurea agonists of the pancreatic KATP channel.

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-ß 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.

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

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.

[Comparative analysis of the efficacy of iodine prophylaxis in pregnant women living in endemic goiter areas]. / Sravnitel'nyi analiz éffektivnosti metodov iodnoi profilaktiki u beremennykh v usloviiakh zobnoi éndemii.

AIM: To assess efficacy of different methods of iodine prophylaxis in pregnant women living in conditions of goiter endemia. MATERIAL AND METHODS: Standard clinical, laboratory and device tests for iodine deficiency according to WHO criteria were made in 156 pregnant women living in the territory affected by goiter endemia. Of them, 121 examinees had no thyroid pathology, 35 ones had diffuse euthyroid goiter. All of them received different kinds of iodine prophylaxis. RESULTS: The occurrence of neonatal TTH values over 5 iU/l in neonates born by mothers free of thyroid pathology on potassium iodide prophylaxis when pregnant was 9.1%. This is much lower than in conventional iodine prophylaxis--17.24% (p < 0.01). A comparative analysis of the efficacy of potassium iodide-200 in pregnant women with diffuse euthyroid goiter and its combination with L-thyroxine has shown that by the effect on lessening frequency of neonatal TTH over 5 iU/l the above schemes do not differ significantly, thyroid reduction is more prominent in pregnant women on thyroxine with potassium iodide. CONCLUSION: The index of neonatal TTH is an objective criterium to control efficacy of different methods of iodine prophylaxis in pregnancy.