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Τετάρτη 5 Απριλίου 2017

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

Abstract

Purpose

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.



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