Case Control Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Sep 15, 2018; 9(9): 157-164
Published online Sep 15, 2018. doi: 10.4239/wjd.v9.i9.157
Association of TCF7L2 mutation and atypical diabetes in a Uruguayan population
Carolina Beloso, Jorge Souto, Matias Fabregat, Gerardo Romanelli, Gerardo Javiel, Adriana Mimbacas
Carolina Beloso, Adriana Mimbacas, Biodiversity and Genetics Department, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo 11600, Uruguay
Jorge Souto, Cytogenetics Laboratory, Hematology and Transplant Service of Hematopoietic Progenitors, Maciel Hospital, ASSE, Montevideo 11600, Uruguay
Jorge Souto, Department of Genetics, Faculty of Medicine, UDELAR, Montevideo 11800, Uruguay
Matias Fabregat, Human Molecular Genetics Laboratory, Institut Pasteur de Montevideo 11400, Uruguay
Gerardo Romanelli, Cell Signaling and Nanobiology Laboratory, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo 11600, Uruguay
Gerardo Javiel, Unit of Diabetes Hospital Pasteur, ASSE-Ministry of Public Health, Montevideo 11400, Uruguay
Gerardo Javiel, Diabetologyc Service of Private Health Center, Centro de Asistencia del Sindicato Médico del Uruguay, Montevideo 11600, Uruguay
Author contributions: Beloso C processed the samples from the atypical diabetes patients and controls, performed analysis and interpretation of the data, and participated in writing of the manuscript; Souto J contributed to laboratory processing of the samples and writing of the manuscript; Fábregat M acquired the patients’ data and performed processing of the “classical” diabetes samples; Romanelli G contributed to the statistical analyses; Javiel G selected the patients for the protocol and attended to them in clinic, and made critical revisions related to the important intellectual content of the manuscript; Mimbacas A made substantial contributions to the conception and design of the study and critical revisions related to the important intellectual content of the manuscript, and gave final approval of the version of the article to be published.
Institutional review board statement: The study was approved by the Ethics Committees of each of the participating institutions (Law 18331).
Informed consent statement: All patients provided written informed consent.
Conflict-of-interest statement: The authors declare that they have no conflicts of interest concerning this article.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Adriana Mimbacas, PhD, Assistant Professor, Biodiversity and Genetics Department, Instituto de Investigaciones Biológicas Clemente Estable, Avenida Italia 3318, Montevideo 11600, Uruguay. amimbacas@iibce.edu.uy
Telephone: +598-2-4861417 Fax: +598-2-4875548
Received: March 22, 2018
Peer-review started: March 22, 2018
First decision: May 16, 2018
Revised: June 6, 2018
Accepted: July 10, 2018
Article in press: July 10, 2018
Published online: September 15, 2018
Processing time: 176 Days and 6.3 Hours
Abstract
AIM

To investigate if mutations in TCF7L2 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 TaqMan® 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 EpiInfo7 statistical packages. Significant statistical differences were assumed in all cases showing adjusted P < 0.05.

RESULTS

We genotyped two TCF7L2 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_TCF7L2 were genotyped in a diabetic population stratified by genotype instead of phenotype. Classical and atypical patients showed statistical differences.

Keywords: TCF7L2; Atypical diabetes; Type 2 diabetes; Latin America; TaqMan

Core tip: This is the first time single nucleotide polymorphisms (SNPs) of the TCF7L2 gene were genotyped and comparatively assessed in Uruguayan type 2 diabetes patients with ”atypical” and “classical” cases. The results show that these two populations are genotypically different. The only statistical association found involved one of the SNPs, rs12255372, and classical diabetes. No association was found to exist between either of the two SNPs examined (rs7903146 and rs12255372) and atypical diabetes. The findings in this study confirm the results of our previous investigations, which indicated that atypical and classical diabetes are two separate entities of the diabetes disease.