High frequency of vitamin D receptor gene polymorphism FokI in Brazilian Type 1 diabetes mellitus patients with clinical autoimmune thyroid disease

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.

Inherited Variation in Vitamin D Genes and Type 1 Diabetes Predisposition

“…To date, there are 65 publications [19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83] on the association of VDR gene SNPs in T1D: these include case-control datasets [20,22,23,25,26,27,28,…”

“…A total of 39 publications support an association between VDR SNPs rs7975232 ( ApaI ), rs1544410 ( BsmI ), rs731236 ( TaqI ) and rs10735810 ( FokI ) alone or in combination with each other, (rs757343 Tru9I , rs1540339 and rs4760648) and T1D [19,21,22,23,24,26,27,28,29,30,34,35,36,37,38,40,41,42,43,44,46,48,49,50,52,53,55,56,59,60,61,62,63,65,68,69,70,71,73] (Table 2) in comparison with 16 studies that refute it [20,25,31,32,39,45,47,51,54,57,58,64,66,67,72,74]. …”

“…To date, there are 65 publications [ 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , <...>…”

“…In contrast, studies from Egypt, Italy and Croatia [ 35 , 41 , 68 ] observed an association with the “ff” genotype and T1D risk. Mory et al (2016) [ 73 ] found homozygous “ff” to be more frequent in T1D subjects with thyroid antibodies (Abs) and thyroid dysfunction in Brazil. T1D patients carrying the rs10735810 ( FokI ) SNP with thyroid peroxidase Abs showed an 18-fold risk to develop thyroid dysfunction.…”

Polymorphisms of the Toll-Like Receptor-2 Gene in Patients with Leprosy and Their Healthy Contacts

“…When there is no mutation (C/C genotype), IL-12 levels are higher than IL-10 levels, however in the presence of the mutation (C/T and T/T genotypes) the opposite happens. IL-10 is a macrophage-suppressing cytokine found in greater quantities in patients with HV, while IL-12 stimulates the production of IFN-γ, induces Th differentiation to become Th1 and is found in greater quantities in HT patients[4] [5].…”