http://orcid.org/0000-0002-6800-8936
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ABSTRACT
Hashimoto’s thyroiditis (HT), the most frequent autoimmune thyroid disease (AITD), is characterized by chronic inflammation of the thyroid gland that usually results in hypothyroidism. Thyroid-stimulating hormone (TSH) and free thyroxine (FT4) levels are used as clinical determinants of thyroid function. The main aim of this study was to explore the association of established TSH and FT4 genetic variants with HT. We performed a case–control analysis using 23 genetic markers in 200 HT patients and 304 controls. Additionally, we tested the association of selected variants with several thyroid-related quantitative traits in HT cases only. Two genetic variants showed nominal association with HT: rs11935941 near NR3C2 gene (p = 0.0034, OR = 0.57, 95% CI = 0.39–0.83) and rs1537424 near MBIP gene (p = 0.0169, OR = 0.72, 95% CI = 0.55–0.94). Additionally, three SNPs showed nominal association with thyroglobulin antibody (TgAb) levels: rs4804416 in INSR gene (p = 0.0073, β = −0.51), rs6435953 near IGFBP5 gene (p = 0.0081, β = 0.75), and rs1537424 near MBIP gene (p = 0.0117, β = 0.49). GLIS3 genetic variant rs10974423 showed nominal association with thyroid peroxidase antibody (TPOAb) levels (p = 0.0465, β = −0.56) and NRG1 genetic variant rs7825175 was nominally associated with thyroid gland volume (p = 0.0272, β = −0.18). All detected loci were previously related to thyroid function or pathology. Findings from our study suggest biological relevance of NR3C2 and MBIP with HT, although these loci require additional confirmation in a larger replication study.
Declaration of interest
The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
Funding
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 THs and antibodies in the 10,001 Dalmatians cohort was supported by the Croatian Science Foundation (grant no. 1498).