Abstract
BackgroundPolymorphisms of vitamin D receptor (VDR) gene have been studied as genetic markers of type 1 diabetes mellitus (T1DM) and some studies have reported associations with autoimmune thyroid disease. The aim of this study was to evaluate the relationship between VDR FokI polymorphism (rs10735810), thyroid autoimmunity and thyroid dysfunction (TD) in Brazilian T1DM.MethodsOne-hundred-eighty T1DM patients were evaluated for age, duration of diabetes (DDM), positivity to TPO Antibody (TPOA), GAD Antibody (GADA), IA2 Antibody (IA2A) and fasting serum C-peptide (FCP) according to diagnosis of TD. PCR–RFLP analyses were carried out for VDR polymorphism FokI.ResultsTPOA positivity (80.0 vs. 25.0 %, p < 0.001) and GADA positivity (56.0 vs. 30.3 %, p = 0.01) were higher in T1DM patients with TD with the same age and DDM than the group without TD, with no difference of FCP and IA2A positivity. We observed higher prevalence of VDR FokI in T1DM with TD (ff and Ff 73.9 % with TD vs. 52.7 % without TD, p = 0.05). Positivity to TPOA and presence of FokI polymorphism were significantly associated with the concurrence of TD in T1DM patients (OR 18.1; CI 3.7–87.0; p < 0.001).ConclusionsThe VDR FokI polymorphism (rs10735810) was associated to persistence of GADA, TPOA positivity and TD in Brazilian T1DM. Positivity to TPOA and VDR polymorphism FokI were strongly associated with concurrence of T1D and TD. These data collaborate to understanding the joint susceptibility genes for TD in T1DM.
Highlights
Polymorphisms of vitamin D receptor (VDR) gene have been studied as genetic markers of type 1 diabetes mellitus (T1DM) and some studies have reported associations with autoimmune thyroid disease
Studies showed that human leukocytes antigen (HLA) class II genes, cytotoxic T-lymphocyte –associated antigen (CTLA-4), protein tyrosine phosphatase (PTNP22) and forkhead box P3 (FOXP3) contribute to susceptibility to both, T1DM and autoimmune thyroid disease (AITD) [7, 8, 11,12,13]
TPO Antibody (TPOA) was positive in 32.6 % (58/178) patients and thyroid dysfunction (TD) was observed in 14 % (25/178)
Summary
Polymorphisms of vitamin D receptor (VDR) gene have been studied as genetic markers of type 1 diabetes mellitus (T1DM) and some studies have reported associations with autoimmune thyroid disease. Type 1 diabetes mellitus (T1DM) often is associated to other autoimmune diseases, and the most frequent observed is autoimmune thyroid disease (AITD) [1,2,3,4]. Fifteen to 30 % of T1DM patients have autoimmune thyroid disease, as well as, 8 % of their first-degree relatives, showing an increased risk for autoimmune disease. Studies showed that HLA class II genes, CTLA-4, PTNP22 and FOXP3 contribute to susceptibility to both, T1DM and AITD [7, 8, 11,12,13]. All of them expressed on activated CD4+ and CD8+ with a role in
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