Polymorphisms in genes encoding miR-155 and miR-146a are associated with protection to type 1 diabetes mellitus
- 620 Downloads
Type 1 diabetes mellitus (T1DM) is characterized by severe autoimmune destruction of pancreatic beta-cells. The triggering of autoimmunity against beta-cells is probably caused by a combination of environmental and genetic risk factors. Even though much is known about the genetic of T1DM, more information is needed to completely unravel this tangled disease. MicroRNAs (miRNAs) are a class of small noncoding RNAs molecules that negatively regulate gene expression by inducing target mRNA cleavage or by inhibiting protein translation. Abnormal miRNA expressions have been described in autoimmune diseases and T1DM. Polymorphisms in genes codifying miRNAs may alter the expression of the corresponding miRNA and, thus, confer susceptibility for a given disease. Therefore, the aim of this study was to investigate whether polymorphisms in genes encoding miR-155, miR-146a, and miR-375 are associated with T1DM.
Frequencies of the miRNA-146a rs2910164, miRNA-155 rs767649 and miRNA-375 rs6715345 polymorphisms were analyzed in 490 T1DM patients and in 469 nondiabetic subjects.
The miR-146a rs2910164 and miR-155 rs767649 polymorphisms were associated with protection for T1DM, and the strongest association was observed for the dominant model [odds ratio (OR) = 0.557 95% CI 0.355–0.874 and OR = 0.508, 95% CI 0.265–0.973, respectively, after adjustment for age, ethnicity, and risk HLA loci]. However, miR-375 rs6715345 frequencies did not differ between cases and controls.
MiR-146a rs2910164 and miR-155 rs767649 polymorphisms were associated with protection for T1DM.
KeywordsType 1 diabetes mellitus Polymorphisms MicroRNA
This study was supported by grants from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (Grant No. 482525/2013-4), Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (Grant No. 1928-2551/13-2), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, and Fundo de Incentivo à Pesquisa e Eventos at Hospital de Clínicas de Porto Alegre (Grant No. 14-0516). D. Crispim, L. H. Canani, and T. S. Assmann are recipients of scholarships from CNPq.
Compliance with ethical standards
Conflict of interest
All authors declare no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the Hospital de Clínicas de Porto Alegre research committee (Number of Approval 14-0516) and with the 1964 Helsinki declaration and its amendments or comparable ethical standards.
All subjects gave assent and written informed consent prior to participation.
- 22.Nielsen LB, Wang C, Sorensen K et al (2012) Circulating levels of microRNA from children with newly diagnosed type 1 diabetes and healthy controls: evidence that miR-25 associates to residual beta-cell function and glycaemic control during disease progression. Exp Diabetes Res 2012:896362. doi: 10.1155/2012/896362 CrossRefPubMedPubMedCentralGoogle Scholar
- 62.El Ouaamari A, Baroukh N, Martens GA, Lebrun P, Pipeleers D, van Obberghen E (2008) miR-375 targets 3′-phosphoinositide-dependent protein kinase-1 and regulates glucose-induced biological responses in pancreatic beta-cells. Diabetes 57(10):2708–2717. doi: 10.2337/db07-1614 CrossRefPubMedPubMedCentralGoogle Scholar