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©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
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
ARTICLE HIGHLIGHTS
Research background
In a high percentage of patients, clinical presentation alone does not define the type of diabetes. This is very important, since it hinders implementation of an individualized and safe treatment. The current classification system of diabetes is useful and easy for typical patients. However, there are many situations in which it is difficult to determine what type of diabetes is presenting due to the great heterogeneity in the pathogenesis. The current classification of diabetes is not satisfactory and its revision has been under consideration for many years. Previous studies carried out in the Uruguayan population have demonstrated the existence of patients for who it is not possible to classify into any of the categories provided in the international guidelines. We continue to investigate this type of patient because it is very important to assist them appropriately and improve their quality of life. In this way, it is possible to abolish the trial stage and error that patients suffer from when not being correctly diagnosed. At this time, different researchers have proposed that the classifications of diabetes should be revised, and this is the principal objective of our work. We have emphatically proposed the inclusion of genetics determination for HLA to elucidate atypical diabetes patients. Such an approach and related data will permit correct classification and treatment for these kinds of patients.
Research motivation
To date, we have investigated genes related to type 1 diabetes in patients with atypical diabetes. In this study, we sought to analyze the major gene related to type 2 diabetes, the TCF7L2 gene, in the atypical diabetes patients.
Research objectives
To analyze the association of the two most important single nucleotide polymorphisms (SNPs) of the TCF7L2 gene-rs12255372 and rs7903146-with atypical diabetes.
Research methods
This case-control study was conducted in atypical and classical cases of type 2 diabetes using genotypification with TaqMan probes for the rs12255372 and rs7903146SNPs of the TCF7L2 gene.
Research results
The SNPs of the TCF7L2 gene that were analyzed in this work showed no association with atypical diabetes; nevertheless, the rs12255372 SNP was associated with classical diabetes.
Research conclusions
As has been shown in previous studies, the genetics of atypical diabetes are different from those of classical diabetes, despite a shared phenotype.
Research perspectives
To continue the characterization of the atypical diabetes subpopulation it will be important to obtain measurements of C-peptide in these patients and to study if there is any difference for this marker between the populations classified.
