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.

To study the association with diabetes mellitus type 1 (T1DM) we performed TDT analysis and analysis of the distribution of frequencies of alleles and genotypes of polymorphic marker C1858T of the PTPN22 gene, encoding tyrosine phosphatase of non-receptor type (LYP). Groups of concordant (27 families) and discordant (62 families) sibpairs and groups of T1DM patients and unrelated controls of Russian origin were recruited in Endocrinology Research Center, Moscow and Center of Diabetes, Samara. For a given polymorphic marker was not found statistically significant associations with type 1 diabetes in the transmission disequilibrium test, while analysis of the distribution of frequencies of alleles and genotypes showed the association with T1DM. Thus, the polymorphic marker C1858T of the PTPN22 gene is associated with T1DM in Russian patients.

Materials and methods. HLA genotyping was accomplished in 51 DM1 patients and 51 volunteers randomly selected from the indigenous populationof Yakutia (Yakuts in three successive generations). Another 205 DM1 patients and 300 healthy subjects comprised random samples of patients andcontrols respectively from residents of Moscow and Moscow region. Results. HLA DRB1*17(03) allele proved to be the strongest one predisposing to DM1 in the Yakutian population (relative risk, RR=8,47) andDQB1*0304 in the Moscow population (RR=8,94). The presence of DRB1*04, DRB1*17(03), DQA1*0301, DQB1*0201, and DQB1*0302 accountedfor RR >2 in both populations. Only two alleles, DRB1*04 and DRB17(03), in the Yakutian population and five of the six (DRB1*04,DRB1*17(03), DQA1*(0301), DQB1*0302, and DQB1*0304) in the Moscow one were closely associated with DM1 (RR >4). DRB1*09, DRB1*11,DQB1*13, DQB1*0602/8 in Yakutian and DRB1*11, DRB1*13, DQA1*0103, DQB1*0301, DQB1*0602/8 in Moscow populations had the highestprotective potential (RR

Aim. To consider association of type 1 diabetes mellitus (DM1) with polymorphous alleles of HLA-DRB1 HLA-DQB1, and DQA1 genes in two Russian populations of Moscow (MP) and Vologda (VP) regions. Materials and methods. Identification of alleles of HLA-DRB1 HLA-DQB1, and DQA1 genes in 138 patients with type 1 diabetes and a random sample of 242 subjects from the local population (residents in at least three successive generations) of the Vologda region, 204 patients and a random sample of 300 subjects from the city of Moscow and Moscow region. Results. MP and VP exhibited identical predisposing alleles. The occurrence of DRB1*4 (RR=5.96 and 3.93 in MP and VP respectively), DRB1*17 (RR=4.33 and 4.23), DQA1*0301 (RR=5.70 and 3.66), DQB1*0201, (RR=2.06 and 1.77), DQB1* 0302 (RR=7.10 and 3.95), DQB1* 0304 (RR=8.94 and 19.98) alleles was significantly higher in DM1 patients. The following protective alleles were identified in MP and VP respectively: DRB1*7 (RR=0.37 and 0.18), DRB1*11 (RR=0.12 and 0.21), DRB1*13 (RR=0.09 and 0.26), DRB1*15 (RR=0.23 and 0.04), DQA1*0102 (RR=0.29 and 0.23), DQA1*0103 (RR=0.13 and 0.23), DQA1*0201 (RR=0.37 and 0.17), DQb1*0301 (RR=0.16 and 0.24), and DQB1*0602/8 (RR=0.10 and 0.13). Conclusion. ?New? associations unknown in other populations (e.g. DQB1*0304) were revealed, besides the majority of classical predisposing and protective alleles characteristic of European populations. DQB1*0304 proved the strongest predisposing allele in MP and especially in VP. These data suggest different contribution of predisposing alleles to the development of DM1 in individual populations.

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.

To map human chromosome 2 region associated with type 1 diabetes mellitus, 89 families with concordant and discordant sib pairs were analyzed. Linkage and association with type 1 diabetes were examined using polymorphic microsatellite markers spanning the region of about 4 Mb. The linkage plot was constructed, and association of the five microsatellite markers within the chromosomal region 2q35 was examined. Polymorphic marker D2S137 (Z′ = 3.225, pc = 0.0048) demonstrated maximum linkage and association with type 1 diabetes.

Цель. Исследовать возможное влияние локуса IDDM18 на предрасположенность к СД1 в семьях из русской популяции. Материалы и методы. Исследованы ДНК двух групп семей из городских популяций Москвы и Самары, с конкордантными (27 семей) и дискордантными (62 семьи) парами сибсов. Выделяли геномную ДНК из крови больных, определяли генотипы полиморфных маркеров. Амплифицированные фрагменты ДНК, содержащие полиморфные маркеры, разделяли в 10% полиакриламидном геле с последующей окраской азотнокислым серебром. Фрагменты ДНК, содержащие полиморфные маркеры, амплифицировали с помощью ПЦР и затем инкубировали в течение 2?4 ч с рестриктазой, расщепляющей данный фрагмент в случае наличия в нем аллеля A. Анализ ассоциации конкордантных и дискордантных семей проводили с использованием объединенного теста TDT (Transmission Disequlibrium Test) и S-TDT (Sib Transmission Disequlibrium Test). Результаты. Ни для одного из исследованных полиморфных маркеров не было показано предположительного сцепления (MLS>2,20) с СД1 в популяции больных русского происхождения. Статистически значимая ассоциация не была показана ни для одного из исследованных маркеров. Таким образом, тест TDT подтвердил отсутствие связи локуса IDDM18 с СД1 в русской популяции больных. Выводы. У больных СД1 русского происхождения не обнаружено сцепления и ассоциации локуса IDDM18 с заболеванием.

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.