engleski

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

Aim: Hashimoto’s thyroiditis (HT) is a chronic autoimmune disease of the thyroid gland, with 8 times higher incidence in women. It is the most common cause of hypothyroidism. Recently, two genome-wide association analyses showed association of several genetic variants with 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. Materials and 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 gland volume) in HT cases only using linear regression. Power of the study was calculated using Quanto and all association analyses were performed using Plink and R statistical software. 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, SE=0.19) and rs4979402 inside DFNB31 gene was nominally associated with TgAb levels (P=0.0443, β=0.41, SE=0.2). There were no significant associations with thyroid gland volume. Conclusion: Our findings suggest that SH2B3 and PDE8B genetic variants are associated with HT. 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

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