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Association of TCF7L2 mutation and atypical diabetes in a Uruguayan population

World Journal of Diabetes 2018年第9期9卷 157-164页

作者： Carolina Beloso Jorge Souto Matias Fábregat gerardo Romanelli gerardo javiel Adriana Mimbacas Biodiversity and Genetics Department Instituto de Investigaciones Biológicas Clemente Estable Cytogenetics Laboratory Hematology and Transplant Service of Hematopoietic Progenitors Maciel Hospital ASSE Department of Genetics Faculty of Medicine UDELAR Human Molecular Genetics Laboratory Institut Pasteur de Montevideo Cell Signaling and Nanobiology Laboratory Instituto de Investigaciones Biológicas Clemente Estable Unit of Diabetes Hospital Pasteur ASSE-Ministry of Public Health Diabetologyc Service of Private Health Center Centro de Asistencia del Sindicato Médico del Uruguay

AIM To investigate if mutations in TCF7 L2 are associated with "atypical diabetes" in the Uruguayan *** Healthy, nondiabetic controls(n = 133) and patients with type 2 diabetes(n = 177) were selected from among the presenting population at level-3 referral healthcare centers in Uruguay. Patients with type 2 diabetes were subgrouped according to "atypical diabetes"(n = 92) and "classical diabetes"(n = 85). Genotyping for the rs12255372 and rs7903146 single nucleotide polymorphisms(SNPs) in the TCFTL2 gene was carried out with Taq Man? probes. Random samples were sequenced by Macrogen Ltd.(South Korea). Statistical analysis of the SNP data was carried out with the SNPStats online tool(http://***/SNPstats). The best inheritance model was chosen according to the lowest values of Akaike's information criterion and Bayesian information criterion. Differences between groups were determined by unpaired t-tests after checking the normal distribution or were converted to normalize the data. The association of SNPs was tested for matched case-control samples by using χ2 analysis and calculation of odds ratios(ORs) with 95% confidence intervals(CIs). All statistical tests were performed using SPSS v10.0 and EpiI nfo7 statistical packages. Significant statistical differences were assumed in all cases showing adjusted P < *** We genotyped two TCF7 L2 SNPs(rs7903146 and rs12255372) in a population-based sample of 310 Uruguayan subjects, including 133 healthy control subjects and 177 clinical diagnosed with type 2 diabetes. For both SNPs analyzed, the best model was the dominant type: rs12255372 = G/G vs G/T+T/T, OR = 0.63, 95%CI: 0.40-0.98, P < 0.05 and rs7903146 = C/C vs C/T+T/T, OR = 0.79, 95%CI: 0.41-1.55, P = 0.3. The rs12255372 SNP showed high association with the type 2 diabetes cases(OR = 1.60, 95%CI: 1.20-2.51, P < 0.05). However, when the type 2 diabetics group was analyzed according to the atypical and classical subgroupings, t

关键词： TCF7L2 Atypical diabetes Type 2 diabetes Latin America TaqMan

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HLA alleles may serve as a tool to discriminate atypical type 2 diabetic patients

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World Journal of Diabetes 2014年第5期5卷 711-716页

作者： Mariana Fernández Matías Fabregat gerardo javiel Adriana Mimbacas Biodiversity and Genetic Department Instituto de Investigaciones Biológicas Clemente Estable Montevideo CP 11600 Uruguay Unit of Diabetes Hospital Pasteur ASSE-Ministry of Public Health Montevideo CP 11400 Uruguay Diabetologyc Service of Private Health Center Centro de Asistencia del Sindicato Médico del Uruguay (CAS-MU) Montevideo CP 11600 Uruguay

AIM: To investigate whether the presence of human leukocyte antigen(HLA) marker could add new information to discriminated atypical diabetic type 2 ***: We analyzed 199 patients initially diagnosed as type 2 diabetes who are treated in special care diabetes clinics(3rd level). This population was classified in "atypical"(sample A) and "classic"(sample B) according to HLA typing. We consider "classic patient" when has absence of type 1 diabetes associated HLA alleles and no difficulties in their diagnosis and treatments. By the other hand, we considered "atypical patient" when show type 1 diabetes associated HLA alleles and difficulties in their diagnosis and treatments. The standard protocol Asociacion Latinoamericana de Diabetes 2006 was used for patients follow up. To analyze differences between both populations in paraclinical parameters we used unpaired t tests and contingence tables. Bivariate and multivariate analyses were carried out using the SPSS software program. In all studies we assume differences statistically significant, with a P-value < 0.05 corrected and 95%***: The typing HLA in the "atypical" populations show that 92.47% patients presented at list one type 1 diabetes associated HLA alleles(DQB1*0201-0302 and DR 3-4) and 7.53% had two of its. The results showed for categorical variables(family history, presence or absence of hypertension and/or dyslipidemia, reason for initial consultation) the only difference found was at dyslipidemia(OR = 0.45, 0.243 < OD < 0.822(P < 0.001). In relation to continuous variables we found significant differences between atypical vs classic only in cholesterol(5.07 ± 1.1 vs 5.56 ± 1.5, P < 0.05), high density lipoproteins(1.23 ± 0.3 vs 1.33 ± 0.3, P < 0.05) and low density lipoproteins(2.86 ± 0.9 vs 3.38 ± 1.7, P < 0.01). None of the variables had discriminating power when logistic regression was ***: We propose an algorithm including HLA genotyping as a tool to discriminate atypical p

关键词： Atypical diabetes Clinical algorithm Immunity molecular marker

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