Search

We tested associations between 13 established genetic variants and type 2 diabetes (T2D) in 1371 study participants from the Volga-Ural region of the Eurasian continent, and evaluated the predictive ability of the model containing polygenic scores for the variants associated with T2D in our dataset, alone and in combination with other risk factors such as age and sex. Using logistic regression analysis, we found associations with T2D for the CCL20 rs6749704 (OR = 1.68, PFDR = 3.40 × 10−5), CCR5 rs333 (OR = 1.99, PFDR = 0.033), ADIPOQ rs17366743 (OR = 3.17, PFDR = 2.64 × 10−4), TCF7L2 rs114758349 (OR = 1.77, PFDR = 9.37 × 10−5), and CCL2 rs1024611 (OR = 1.38, PFDR = 0.033) polymorphisms. We showed that the most informative prognostic model included weighted polygenic scores for these five loci, and non-genetic factors such as age and sex (AUC 85.8%, 95%CI 83.7–87.8%). Compared to the model containing only non-genetic parameters, adding the polygenic score for the five T2D-associated loci showed improved net reclassification (NRI = 37.62%, 1.39 × 10−6). Inclusion of all 13 tested SNPs to the model with age and sex did not improve the predictive ability compared to the model containing five T2D-associated variants (NRI = −17.86, p = 0.093). The five variants associated with T2D in people from the Volga-Ural region are linked to inflammation (CCR5, CCL2, CCL20) and glucose metabolism regulation (TCF7L, ADIPOQ2). Further studies in independent groups of T2D patients should validate the prognostic value of the model and elucidate the molecular mechanisms of the disease development.

Background Genome-wide association studies have captured a large proportion of genetic variation related to type 1 diabetes mellitus (T1D). However, most of these studies are performed in populations of European ancestry and therefore the disease risk estimations can be inaccurate when extrapolated to other world populations. Methods We conducted a case-control study in 1866 individuals from the three major populations of the Republic of Bashkortostan (Russians, Tatars, and Bashkirs) in Russian Federation, using single-locus and multilocus approach to identify genetic predictors of T1D. Results We found that LTA rs909253 and TNF rs1800629 polymorphisms were associated with T1D in the group of Tatars. Meta-analysis of the association study results in the three ethnic groups has confirmed the association between the T1D risk and LTA rs909253 genetic variant. LTA rs909253 and TNF rs1800629 loci were also featured in combinations most significantly associated with T1D. Conclusion Our findings suggest that LTA rs909253 and TNF rs1800629 polymorphisms are associated with the risk of T1D both independently and in combination with polymorphic markers in other inflammatory genes, and the analysis of multi-allelic combinations provides valuable insight in the study of polygenic traits.

Type 2 diabetes mellitus (T2DM) is one of the most acute problems of the modern world. The disease is characterized by high ratio of micro- and macrovascular complications. T2DM is a multifactorial and polygenic disease, structure of hereditary predisposition to which may be population-specific. Aim - the analysis of allelic associations of adiponectin gene (ADIPOQ, rs17366743) with T2DM, its clinical and metabolic characteristics and complications in T2DM patients resident in the Republic of Bashkortostan.3 PCR-based method of genotyping with polymorphic marker rs17366743 of ADIPOQ gene in 433 T2DM patients and 428 healthy controls, residents of Bashkortostan.The ratio of genotype CT and allele С was higher in T2DM patients compared with controls (15.7% vs. 6.8%; p=0.0002 and 7.8% vs. 3.4%; p0.0001, respectively). Genotype ТТ and allele Т were less frequent in T2DM than in healthy subjects (84.3 and 93,2%; p=0.0002; 92.2 and 96.6%, p0.0001, respectively). The association with the development of diabetic retinopathy and cataract was shown (p=0,044, p=0,008, respectively).Allele C and genotype CT are risk markers of T2DM (OR=2.43 and 2.56 respectively).Сахарный диабет 2-го типа (СД2) является одной из острейших проблем современного мира. Заболевание характеризуется высокой частотой микро- и макрососудистых осложнений. СД2 — многофакторное полигенное заболевание, структура наследственной предрасположенности к которому может иметь популяционно-специфические особенности. Цель исследования — анализ ассоциаций аллелей гена адипонектина ADIPOQ (rs17366743) с СД2, его клинико-метаболическими характеристиками и осложнениями у жителей Республики Башкортостан. Материал и методы. Генотипирование по полиморфному маркеру rs17366743 гена адипонектина ADIPOQ 433 пациентов с СД2 и 428 здоровых жителей Башкортостана проведено с использованием метода полимеразной цепной реакции (ПЦР) синтеза ДНК. Результаты. В группе пациентов с СД2 выявлена более высокая частота генотипа CT и аллеля С, чем в контрольной группе (15,7% против 6,8%; p=0,0002 и 7,8% против 3,4%; p0,0001 соответственно). Среди пациентов с СД2 генотип ТТ и аллель Т выявлены с меньшей частотой, чем среди здоровых лиц (84,3 и 93,2%; p=0,0002; 92,2 и 96,6%; p0,0001 соответственно). Показана ассоциация изученных генотипов и аллелей с развитием диабетической ретинопатии и катаракты (p=0,044 и p=0,008 соответственно). Заключение. Аллель С и генотип СТ являются маркерами риска развития СД2 (OR=2,43 и 2,56 соответственно).

Aims. To estimate significance of HLA II DRB1 and DRB2 allele variants for development of type 1 diabetes mellitus (T1DM) in Bashkortostanpopulation (ethnical Russians, Tatar, Bashkir). Materials and methods. We analyzed DNA of 323 patients with T1DM and 683 healthy controls. DNA was derived from venous bloodsamples by phenol-chloroform extraction. DRB1 and DQB1 gene typing was performed by PCR method. Amplification products wereidentified with electrophoresis on a 1% agarose gel. Statistica for Windows v6.0 and MS Excel 98 software were applied for statisticalprocessing of acquired data. Results. Common markers of high risk for T1DM were found to be DRB1*04, DRB1*17, genotype DRB1*04/*17. On the contrary,lower risk was associated with DRB1*15 allele. In ethnical Russians lower risk of T1DM is also determined by DRB1*11 allele andDRB1*01 in Tatars. Predisposition by DQB1-alleles in Russians and Bashkir realizes only within DRB1*04/*17 genotype. However,in Tatar subpopulation DQB1*0302 is an independent risk marker of T1DM development. Conclusion. Common low risk markers for all three ethnic groups are DQB1*0301, DQB1*0602-08 alleles. Their presence negates riskof disease in all studied subpopulations even within DRB1*04/*17-genotype.