Association of multiple single nucleotide polymorphisms and autoimmune thyroid disease

Autoimmune thyroid diseases (AITD) are common and affect up to 5% of the general population. AITD are represented by Graves’ disease (GD) and Hashimoto’s thyroiditis (HT) and are multifactorial. It arises from an interplay of genetic, environmental, and immunologic triggers. Thyroid Stimulating Hormone Receptor (TSHR) and Thyroglobulin (Tg) coding genes in chromosomes 14 and 8, respectively, have been described in association with AITD.Aim: to detect thyroglobulin (Tg) and TSHR gene polymorphisms and to study their association with autoimmune thyroid disease (AITD). A total of 1001 subjects were included in a cross-sectional study. They were divided into 3 groups: GD Group, HT Group, and a Control Group. Subjects were diagnosed with AITD based upon laboratory examinations that confirmed thyroid autoimmunity as well as functional disturbances. DNA samples were genotyped using Infinum Global Screening Array, Affymetrix Axiom Genome-Wide, Human EU un OmniExpressExome BeadChips. Association analysis was performed by using PLINK 2.9 and SAIGE. The most significant single nucleotide polymorphism (SNP) associations with AITD in the TSHR gene were rs60227643 (OR=24.13 (95% CI 4.75-122.5), p=0.0001235) and rs144801375 (OR=5.09 (95% CI 2.15-12.05), p=0.0002126). The most significant SNP associations with AITD in the Tg gene were rs2687828 (OR=1.48 (95% CI 1.21-1.81), p=0.000142) and rs2687825 (OR=1.46 (95% CI 1.19-1.79), p= 0.0002106). Tg gene SNPs - rs2687828 and rs2687825 - correlated with GD and HT. We found a previously undescribed strong association of TSHR gene SNPs rs60227643 and rs144801375 and susceptibility for AITD.This study was supported by the Latvian Council of Science (Grant No: lzp-2018/2-0059).