title: Association of established hypothyroidism-associated genetic variants with Hashimoto's thyroiditis.
abstract: OBJECTIVE
  Hashimoto's thyroiditis (HT) as a chronic autoimmune disease of the thyroid gland is the most common cause of hypothyroidism. Since HT and hypothyroidism are closely related, the main aim of this study was to explore the association of established hypothyroidism single-nucleotide polymorphisms (SNPs) with HT.
  
  
  METHODS
  The case-control dataset included 200 HT cases and 304 controls. Diagnosis of HT cases was based on clinical examination, measurement of thyroid antibodies (TgAb, TPOAb), hormones (TSH and FT4) and ultrasound examination. We genotyped and analysed 11 known hypothyroidism-associated genetic variants. Case-control association analysis was performed in order to test each SNP for the association with HT using logistic regression model. Additionally, each SNP was tested for the association with thyroid-related quantitative traits (TPOAb levels, TgAb levels and thyroid volume) in HT cases only using linear regression.
  
  
  RESULTS
  We identified two genetic variants nominally associated with HT rs3184504 in SH2B3 gene (P = 0.0135, OR = 0.74, 95% CI = 0.57-0.95) and rs4704397 in PDE8B gene (P = 0.0383, OR = 1.32, 95% CI = 1.01-1.74). The SH2B3 genetic variant also showed nominal association with TPOAb levels (P = 0.0163, β = -0.46) and rs4979402 inside DFNB31 gene was nominally associated with TgAb levels (P = 0.0443, β = 0.41).
  
  
  CONCLUSIONS
  SH2B3 gene has previously been associated with susceptibility to several autoimmune diseases, whereas PDE8B has been associated with TSH levels and suggested to modulate thyroid physiology that may influence the manifestation of thyroid disease. Identified loci are novel and biologically plausible candidates for HT development and represent good basis for further exploration of HT susceptibility.
authors.affiliation: Department of Nuclear Medicine, University Hospital Split, Split, Croatia.
authors.forename: A
authors.initials: A
authors.lastname: Barić
authors.affiliation: Department of Medical Biology, School of Medicine, University of Split, Split, Croatia.
authors.forename: L
authors.initials: L
authors.lastname: Brčić
authors.affiliation: Department of Nuclear Medicine, University Hospital Split, Split, Croatia.
authors.forename: S
authors.initials: S
authors.lastname: Gračan
authors.affiliation: Department of Nuclear Medicine, University Hospital Split, Split, Croatia.
authors.forename: V
authors.initials: V
authors.lastname: Torlak Lovrić
authors.affiliation: Department of Medical Biology, School of Medicine, University of Split, Split, Croatia.
authors.forename: I
authors.initials: I
authors.lastname: Gunjača
authors.affiliation: Department of Nuclear Medicine, University Hospital Split, Split, Croatia.
authors.forename: M
authors.initials: M
authors.lastname: Šimunac
authors.affiliation: Department of Nuclear Medicine, University Hospital Split, Split, Croatia.
authors.forename: M
authors.initials: M
authors.lastname: Brekalo
authors.affiliation: Department of Pharmacology, School of Medicine, University of Split, Split, Croatia.
authors.forename: M
authors.initials: M
authors.lastname: Boban
authors.affiliation: Department of Public Health, School of Medicine, University of Split, Split, Croatia.
authors.forename: O
authors.initials: O
authors.lastname: Polašek
authors.affiliation: Department of Medical Biology, School of Medicine, University of Split, Split, Croatia.
authors.forename: M
authors.initials: M
authors.lastname: Barbalić
authors.affiliation: Department of Medical Biology, School of Medicine, University of Split, Split, Croatia.
authors.forename: T
authors.initials: T
authors.lastname: Zemunik
authors.affiliation: Department of Nuclear Medicine, University Hospital Split, Split, Croatia.
authors.forename: A
authors.initials: A
authors.lastname: Punda
authors.affiliation: Department of Medical Biology, School of Medicine, University of Split, Split, Croatia. vboraska@mefst.hr.
authors.forename: V
authors.initials: V
authors.lastname: Boraska Perica
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000235:genetics*; D048868:Adaptor Proteins, Signal Transducing; D001323:Autoantibodies / Q000097:blood; D015415:Biomarkers / Q000378:metabolism*; D016022:Case-Control Studies; D005500:Follow-Up Studies; D050031:Hashimoto Disease / Q000150:complications / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007037:Hypothyroidism / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D047908:Intracellular Signaling Peptides and Proteins; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011506:Proteins / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D001323:Autoantibodies; D015415:Biomarkers; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; C490778:SH2B3 protein, human; D015105:3',5'-Cyclic-AMP Phosphodiesterases; C468781:PDE8B protein, human
keywords: Candidate gene study; Genetic epidemiology; Hashimoto’s thyroiditis; Hypothyroidism; Single-nucleotide polymorphism