Association of Established Thyroid-stimulating Hormone and Free Thyroxine Genetic Variants with Hashimoto's Thyroiditis

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...

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Bibliographic Details
Published in:Immunological investigations 2017-08, Vol.46 (6), p.625-638
Main Authors: Brčić, Luka, Gračan, Sanda, Barić, Ana, Gunjača, Ivana, Torlak Lovrić, Vesela, Kolčić, Ivana, Zemunik, Tatijana, Polašek, Ozren, Barbalić, Maja, Punda, Ante, Boraska Perica, Vesna
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Autoantibodies - blood
Case-control association analysis
Case-Control Studies
Croatia - epidemiology
Female
free thyroxine
genetic variants
Hashimoto Disease - blood
Hashimoto Disease - epidemiology
Hashimoto Disease - genetics
Hashimoto's thyroiditis
Humans
Male
MBIP
Middle Aged
NR3C2
Polymorphism, Single Nucleotide
Thyroglobulin - immunology
thyroid-stimulating hormone
Thyrotropin - blood
Thyroxine - blood
Young Adult
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Summary: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.
ISSN:0882-0139
1532-4311
DOI:10.1080/08820139.2017.1337785