A Polymorphism in the Promoter Region of the Selenoprotein S Gene (SEPS1) Contributes to Hashimoto's Thyroiditis Susceptibility

Context: The association between selenium and inflammation and the relevance of selenoproteins in follicular thyroid cell physiology have pointed to a putative role of selenoproteins in the pathogenesis of autoimmune thyroid diseases. Objective: The aim of this study was to evaluate the role of a promoter variation in SEPS1, the selenoprotein S gene, in the risk for developing Hashimoto's thyroiditis (HT). Design: A case-control study was performed to assess the association of genetic variation in the SEPS1 gene (SEPS1 - 105G/A single-nucleotide polymorphism, rs28665122) and HT. Setting: The study was conducted in north Portugal, Porto, in the period of 2007-2013. Patients or Other Participants: A total of 997 individuals comprising 481 HT patients and 516 unrelated controls were enrolled in the study. Main Outcome Measures: Genetic variants were discriminated by real-time PCR using TaqMan single-nucleotide polymorphism genotyping assays. Results: There is a significant association between the SEPS1 - 105 GA and AA genotypes and HT [odds ratio (OR) 2.24, confidence interval (CI) 1.67-3.02, P < 5.0 x 10(-7), and OR 2.08, CI 1.09-3.97, P = .0268, respectively]. The A allele carriers are in higher proportion in the patient group than in the control population (46.2% vs 28.1%, P < 5.0 x 10(-7)) with an OR (CI) of 2.22 (1.67-2.97). The proportion of patients carrying the A allele is significantly higher in male patients with HT, representing a 3.94 times increased risk (P = 7.9 x 10(-3)). Conclusion: Our findings support the existence of a link between SEPS1 promoter genetic variation and HT risk.