Association of TCF7L2 mutation and atypical diabetes in a Uruguayan population

AIM To investigate if mutations in TCF7 L2 are associated with "atypical diabetes" in the Uruguayan population.METHODS 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://bioinfo.iconcologia.net/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 0.05.RESULTS 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, the association with diabetes existed only for rs12255372 and the classical subgroup(vs controls: OR = 2.1, 95%CI: 1.21-3.75, P 0.05); no significant differences were found for either SNP or atypical diabetes.CONCLUSION This is the first time SNPs_TCF7 L2 were genotyped in a diabetic population stratified by genotype instead of phenotype. Classical and atypical patients showed statistical differences.