Journal of Endocrinological Investigation

, Volume 40, Issue 10, pp 1061–1067 | Cite as

Association of established hypothyroidism-associated genetic variants with Hashimoto’s thyroiditis

  • A. Barić
  • L. Brčić
  • S. Gračan
  • V. Torlak Lovrić
  • I. Gunjača
  • M. Šimunac
  • M. Brekalo
  • M. Boban
  • O. Polašek
  • M. Barbalić
  • T. Zemunik
  • A. Punda
  • V. Boraska PericaEmail author
Original Article



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.


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.


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).


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.


Hashimoto’s thyroiditis Hypothyroidism Candidate gene study Genetic epidemiology Single-nucleotide polymorphism 


Compliance with ethical standards

Conflict of interest

The authors declare no conflicts of interest associated with the manuscript. The formation of HT biobank was supported by the Croatian Science Foundation under the project “Genome-wide association analysis of Hashimoto thyroiditis” (Grant No. 4950). The 10,001 Dalmatians project was supported by the MRC Human Genetics Unit, The Croatian Ministry of Science, Education and Sports (Grant 216-1080315-0302), the European Union Framework Program 6 EUROSPAN project (Contract No. LSHG-CT-2006-018947), EU FP7 BBMRI-LPC (Biobanking and biomolecular resources research infrastructure—Large prospective cohort, contract 313010) and the Croatian Science Foundation (Grant 8875). Measurement of thyroid hormones and antibodies in the 10,001 Dalmatians cohort was supported by the Croatian Science Foundation (Grant No. 1498).

Ethical Standards

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.


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Copyright information

© Italian Society of Endocrinology (SIE) 2017

Authors and Affiliations

  • A. Barić
    • 1
  • L. Brčić
    • 2
  • S. Gračan
    • 1
  • V. Torlak Lovrić
    • 1
  • I. Gunjača
    • 2
  • M. Šimunac
    • 1
  • M. Brekalo
    • 1
  • M. Boban
    • 3
  • O. Polašek
    • 4
  • M. Barbalić
    • 2
  • T. Zemunik
    • 2
  • A. Punda
    • 1
  • V. Boraska Perica
    • 2
    Email author
  1. 1.Department of Nuclear MedicineUniversity Hospital SplitSplitCroatia
  2. 2.Department of Medical Biology, School of MedicineUniversity of SplitSplitCroatia
  3. 3.Department of Pharmacology, School of MedicineUniversity of SplitSplitCroatia
  4. 4.Department of Public Health, School of MedicineUniversity of SplitSplitCroatia

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