Hashimoto's thyroiditis (HT) is the most frequent autoimmune thyroid disease with strong genetic background. Vitamin D receptor (VDR) endocrine system affects immunosuppressive, regulatory and tolerogenic decisions required for induction and maintenance of peripheral immune tolerance. With respect to the biological function of the VDR and functionally plausible gene-expression data, we sought to test whether particular 3'-restriction fragment length polymorphisms (RFLP) and haplotypes previously directly or indirectly associated with VDR mRNA 3'-allelic imbalance phenotype and differences in total VDR mRNA expression are implicated in HT susceptibility. Thus, 145 Croatian HT patients and 145 age-, sex- and ethnically matched euthyroid controls were genotyped for VDR rs1544410 (BsmI), rs7975232 (ApaI) and rs731236 (TaqI) polymorphisms by polymerase chain reaction-RFLP method. Covariate-adjusted single-locus and haplotype-phenotype regression analyses were performed. Permutation corrections (P(c)) and Akaike Information Criteria were used for model comparisons. The best-fit [global P(c) = 7.2 x 10(-4)]BsmI-TaqI BT haplotype was found significantly more often in subjects without HT [12.2% vs. 3.7%; odds ratio (OR, 95% confidence intervals) = 0.28 (0.14-0.56), P(c) = 8 x 10(-4)], whereas the bT haplotype was significantly more frequent in individuals with HT [45.7% vs. 61.8%; OR = 1.91 (1.37-2.65), P(c) = 4 x 10(-4)]. Two extended BsmI-ApaI-TaqI RFLP haplotypes, the common baT [35.7 vs. 47.3%, OR = 1.63 (1.17-2.27), P(c) = 0.012] and rare BaT variants [6.5 vs. 1.2%, OR = 0.17 (0.06-0.55), P(c) = 1.2 x 10(-3)] were associated with HT, representing predisposing and protective haplotypes, respectively. In single-RFLP association analyses, only rs1544410 polymorphism was associated with HT phenotype (allelic P(c) = 0.0078) and appeared to function under the recessive model, with decreased risk of HT among the BB homozygotes [OR = 0.39 (0.21-0.7), P(c) = 0.0052] when compared to the reference b(+)-genotypes. These data suggest that common haplotypic variants within the VDR gene 3'-region previously linked to VDR mRNA expression and allelic imbalance could be associated with HT in the general population, and thus, may be involved in the pathogenesis of HT.
Cis-acting regulatory variants in biologically relevant pathways and target tissues are a common source of phenotypic variations and individual disease susceptibility. In the skin, vitamin D receptor (VDR) is a master regulator of epidermal barrier function, inflammation, stem cell proliferation and microbial defense; therefore, we tested whether VDR 3'-regulatory haplotypes, a portion of which affect VDR transcriptional efficiency, allelic symmetry and mRNA turnover, were associated with psoriasis vulgaris. For this purpose, three VDR tag polymorphisms that capture most of the variability of the VDR 3'-regulatory element (rs1544410, rs7975232 and rs731236) were genotyped by the polymerase chain reaction restriction fragment length polymorphism method in 180 Caucasian patients with chronic plaque psoriasis and 366 ethnically matched, healthy controls of the Croatian origin. We found no evidence of association for any of the selected polymorphisms. Similarly, none of the 3'-VDR restriction haplotypes were associated with the risk for development of psoriasis in Croatian patients. These results show that neither VDR 3'-restriction polymorphisms nor common 3'-regulatory haplotypes contribute to psoriasis risk in the Croatian population.
No genetic variant examined in the VDR gene showed a robust and reproducible association with risk for psoriasis. Any association that may exist is likely to be weak and potentially restricted to specific populations.
Hashimoto's thyroiditis (HT) is an organ-specific autoimmune disorder characterized by progressive thyroid failure. Th1 and Treg subset of CD4+ cells have been implicated in the pathogenesis; however, less is known about their respective roles across the spectrum of HT clinical presentations. To shed more light on CD4+ subsets role in HT, we investigated the mRNA expression levels of several Th1/Treg-associated transcription factors (T-bet/ETS1, HIF1α/BLIMP1/FOXP3) in peripheral blood T cells of 10 hypothyroid, untreated HT patients, 10 hypothyroid patients undergoing hormone replacement therapy, 12 euthyroid HT subjects, and 11 healthy controls by the qRT-PCR. Compared to euthyroid HT patients and controls, both hypothyroid (2.34-fold difference versus controls, P < 0.01) and thyroxine-supplemented patients (2.5-fold, P < 0.001) showed an increased FOXP3 mRNA expression in T cells. Similarly, mRNA expression levels of T-bet were upregulated in severely affected but not in euthyroid HT subjects (2.37-fold and 3.2-fold, hypothyroid and thyroxine-supplemented HT patients versus controls, resp., P < 0.01). By contrast, no differences in mRNA expression levels of ETS1, BLIMP1, and HIF1α were observed across the study groups. In summary, severe but not euthyroid HT was associated with robust upregulation of T-bet and FOXP3 mRNA in peripheral T cells, independent of the thyroid hormone status but proportional to disease activity.
Baseline TPOAb positivity is an independent indicator of long-term remission in GD patients who have been successfully treated, but the mechanism of action and causal relations remain unknown.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.