A. G. Nikitin

Association of the PTPN22 polymorphism C1858T with type 1 diabetes mellitus.

PTPN22 encodes a lymphoid protein tyrosine phosphatase LYP. Association of the PTPN22 polymorphism C1858T with type 1 diabetes mellitus was investigated using the transmission disequilibrium test (TDT) and a comparative analysis of the allele and genotype frequency distributions. The study involved two groups of families from Russian populations of Moscow and Samara with concordantly (27 families) and discordantly (62 families) affected sibs, as well as groups of type 1 diabetes patients and healthy individuals. The association of the PTPN22 polymorphism with type 1 diabetes was not significant by TDT analysis, but was significant by comparison of the allele and genotype frequency distributions. Thus, a case-control analysis detected an association of the PTPN22 polymorphism C1858T with type 1 diabetes mellitus in Russians.

Association of the polymorphisms of the ERBB3 and SH2B3 genes with type 1 diabetes

To study the association with diabetes mellitus type 1, we analyzed the distribution of allele and genotype frequencies of polymorphic marker rs2292239 of ERBB3 gene, encoding epidermal growth factor receptor type 3 and polymorphic marker rs3184504 of SH2B3 gene, encoding adaptor protein LNK. The study included groups of T1DM patients and unrelated controls of Russian origin. Genotyping was performed using RFLP and real-time amplification methods. No statistically significant association with type 1 diabetes was found for the polymorphic marker rs2292239 of ERBB3, while the analysis of the distribution of allele and genotype frequencies of the polymorphic marker rs3184504 of SH2B3 gene revealed the association with T1DM in the Russian population.

Association of FTO , KCNJ11 , SLC30A8 , and CDKN2B polymorphisms with type 2 diabetes mellitus

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.

Sex determination in biological specimens using the DYS14 marker

The applicability of real-time PCR amplification of the chromosome Y marker DYS14 for sex determination was studied. With this aim, real-time PCR of DYS14 (located within the TSPY1-encoding gene) was performed in plasma DNA specimens obtained from 30 men and 30 women. The PCR results showed that 30 specimens were of male and the other 30 were of female origin. All the results were confirmed by the tests for the SRY marker conventionally used in forensic examination. The detection limit for the DYS14-containing DNA region was established in dilution experiments and was equal to 6.7 pg of DNA (two copies of the genome), which corresponds to 6.7 ng of DNA (2000 copies of the genome) in 1 ml of blood. This level of sensitivity allows sex determination in specimens with small amounts of genetic material. The method can be used for noninvasive prenatal diagnostics of sex-linked congenital diseases and in forensic medical examination.

Genetic factors in the development of chronic kidney disease in patients with diabetes mellitus

Patients with diabetes mellitus (DM) represent a risk group for developing chronic kidney disease (CKD), the terminal stages of which require renal replacement therapy. The study of genetic predisposition to CKD is of special significance from the perspective of the prediction and identification of risk groups at the preclinical stage. The present study is a review of the world literature on the genetics of CKD in diabetes and also includes data of our own studies.

Association of polymorphic markers of genes FTO, KCNJ11, CDKAL1, SLC30A8, and CDKN2B with type 2 diabetes mellitus in the Russian population

Background The association of type 2 diabetes mellitus (T2DM) with the KCNJ11, CDKAL1, SLC30A8, CDKN2B, and FTO genes in the Russian population has not been well studied. In this study, we analysed the population frequencies of polymorphic markers of these genes. Methods The study included 862 patients with T2DM and 443 control subjects of Russian origin. All subjects were genotyped for 10 single nucleotide polymorphisms (SNPs) of the genes using real-time PCR (TaqMan assays). HOMA-IR and HOMA-β were used to measure insulin resistance and β-cell secretory function, respectively. Results The analysis of the frequency distribution of polymorphic markers for genes KCNJ11, CDKAL1, SLC30A8 and CDKN2B showed statistically significant associations with T2DM in the Russian population. The association between the FTO gene and T2DM was not statistically significant. The polymorphic markers rs5219 of the KCNJ11 gene, rs13266634 of the SLC30A8 gene, rs10811661 of the CDKN2B gene and rs9465871, rs7756992 and rs10946398 of the CDKAL1 gene showed a significant association with impaired glucose metabolism or impaired β-cell function. Conclusion In the Russian population, genes, which affect insulin synthesis and secretion in the β-cells of the pancreas, play a central role in the development of T2DM.

The analysis of association between type 2 diabetes and polymorphic markers in the CDKAL1 gene and in the HHEX/IDE locus

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.

Polymorphic gene markers ILRA and IL2: population distinctions in association with diabetes mellitus

Aims. In order to study type 1 diabetes mellitus associations, we conducted a comparative analysis of allele and genotype frequencydistribution of polymorphic markers rs41295061 and rs11594656 of IL2RA gene, which encodes ?-chain of interleukin-2receptor, - and rs2069762, a marker of IL2, gene, encoding interleukin-2. Materials and methods. Experimental group included 451 patients with type 1 diabetes mellitus (DM); control group consistedof 306 healthy subjects (both groups were represented by ethnic Russians). Alleles and polymorphic markers were identified byreal-time amplification method. Results. A comparative analysis of patients with type 1 DM and healthy control group did not show statistically significant differencesfrom the viewpoint of allele and genotype frequency distribution of polymorphic markers rs41295061, rs11594656 andrs2069762. This makes Russian patients considerably different from European ones where markers in question show substantialassociation with type 1 DM. Conclusion. A comparative analysis of allele and genotype frequency distribution of IL2-RA and IL2 genes polymorphic markersshowed population differences in association of these markers in Russian and European patients.

Association of -23 HphI, a polymorphic marker of the INS gene, with type 1 diabetes mellitus

Aim. To analyse frequency distribution of alleles and genotypes of -23 HphI, a polymorphic marker of the INS gene, for evaluation of its associationwith DM1. Materials and methods. The study included two group of subjects: healthy ones and DM1 patients. Genotyping was performed by real time amplification. Results. Comparative analysis demonstrated association between -23 HphI polymorphic marker of INS gene, and type 1 diabetes mellitus. Conclusion. The use of the case-control method revealed association of -23 HphI, a polymorphic marker of the INS gene, with type 1 diabetes mellitus.

Sindrom Al'strema u podrostkov (pervoe opisanie v Rossii)

Синдром Альстрема впервые был описан в 1959 г. Основными симптомами этого прогрессирующего аутосомно-рецессивного расстройства являются врожденная дегенерация сетчатки, ведущая к слепоте, детское ожирение, сахарный диабет 2 типа (СД2). Заболевание встречается среди различных рас и этнических групп. Известны ядерные семьи (2?3 пораженных ребенка). Частота синдрома в популяции остается неизвестной. Полиморфизм клинической картины синдрома Альстрема, сходной с многими другими генетическими синдромами, затрудняет диагностику. Однако молекуляно-генетические исследования способствуют раннему выявлению данного синдрома.