Polymorphisms in the TLR3 gene are associated with risk for type 1 diabetes mellitus

• Published in: European journal of endocrinology Vol. 170; no. 4; pp. 519 - 527
• Main Authors: Assmann, Taís Silveira, Brondani, Letícia de Almeida, Bauer, Andrea Carla, Canani, Luis Henrique, Crispim, Daisy
• Format: Journal Article
• Language: English
• Published: Bristol Bioscientifica Ltd 01.04.2014; BioScientifica
• Subjects: Adult; Bayes Theorem; Biological and medical sciences; Case-Control Studies; Clinical Study; Diabetes Mellitus, Type 1 - genetics; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Fundamental and applied biological sciences. Psychology; Gene Frequency; Genetic Predisposition to Disease; Genotype; Haplotypes; Humans; Male; Medical sciences; Middle Aged; Polymorphism, Single Nucleotide; Toll-Like Receptor 3 - genetics; Vertebrates: endocrinology; Young Adult; Endocrinopathy; Immunopathology; Association; Gene; Type 1 diabetes; Risk factor; Genetics; Autoimmune disease; Risk; Endocrinology; Polymorphism
• DOI: 10.1530/EJE-13-0963
• ISSN: 0804-4643; 1479-683X

IntroductionViral pathogens seem to play a role in triggering the autoimmune destruction that leads to the development of type 1 diabetes mellitus (T1DM). Toll-like receptor 3 (TLR3) has been shown to recognize double-stranded RNA, a molecular signature of most viruses. It is expressed at high levels in pancreatic β-cells and immune cells, suggesting a role for it in the pathogenesis of T1DM. Therefore, the aim of this study was to investigate whether TLR3 polymorphisms are associated with T1DM.MethodsFrequencies of the TLR3 rs11721827, rs13126816, rs5743313, rs7668666, and rs3775291 polymorphisms were analyzed in 449 T1DM patients and in 507 nondiabetic subjects. Haplotypes constructed from the combination of these polymorphisms were inferred using a Bayesian statistical method.ResultsThe rs3775291 and rs13126816 polymorphisms were associated with T1DM, and the strongest association was observed for the additive model (odds ratio (OR)=2.3, 95% CI 1.3–4.2 and OR=2.1, 95% CI 1.3–3.1 respectively). In the same way, the frequency of T1DM was higher as more risk alleles of the five polymorphisms were present (P-trend=0.001). Moreover, in T1DM patients, the minor alleles of the rs5743313 and rs117221827 polymorphisms were associated with an early age at diagnosis and worse glycemic control.ConclusionThe TLR3 rs3775291 and rs13126816 polymorphisms are associated with risk for T1DM, while the rs5743313 and rs11721827 polymorphisms are associated with age at T1DM diagnosis and poor glycemic control. The number of risk alleles of the five TLR3 polymorphisms in the haplotypes seems to influence the risk for T1DM, suggesting that these polymorphisms might interact in the susceptibility for the disease.