A polymorphism in the promoter region of the selenoprotein S gene (SEPS1) contributes to Hashimoto's thyroiditis susceptibility.
BACKGROUND
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).


METHODS
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.


METHODS
The study was conducted in north Portugal, Porto, in the period of 2007-2013.


METHODS
A total of 997 individuals comprising 481 HT patients and 516 unrelated controls were enrolled in the study.


METHODS
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 × 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 × 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 × 10(-3)).


CONCLUSIONS
Our findings support the existence of a link between SEPS1 promoter genetic variation and HT risk.
Faculty of Medicine (L.R.S.), University of Coimbra, 3000-214 Coimbra, Portugal; Institute of Molecular Pathology and Immunology of University of Porto (L.R.S., C.D., A.M., H.P., M.I.A., C.S.M., P.C., M.S-S., P.S.), Faculty of Medicine (H.P., C.S.M., P.C., C.N., D.C., M.S.S., P.S.), and Department of Pathology and Oncology (M.S.S., P.S.), Faculty of Medicine, University of Porto, 4200-465 Porto, Portugal; and Department of Endocrinology (C.E., C.N., D.C.), Hospital of S. João, 4200-319 Porto, Portugal.
Liliana R
LR
Santos
Cecília
C
Durães
Adélia
A
Mendes
Hugo
H
Prazeres
Maria Inês
MI
Alvelos
Carla Susete
CS
Moreira
Paulo
P
Canedo
César
C
Esteves
Celestino
C
Neves
Davide
D
Carvalho
Manuel
M
Sobrinho-Simões
Paula
P
Soares
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D050031:Hashimoto Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D051140:Selenoproteins / Q000235:genetics*; D055815:Young Adult
D008565:Membrane Proteins; C487710:SELENOS protein, human; D051140:Selenoproteins