Upmale-Engela Sabine, Vaivode Ieva, Peculis Raitis, Litvina Helena, Zake Tatjana, Skesters Andrejs, Gogins Deniss, Rovite Vita, Konrade Ilze
Department of Internal Medicine, Riga Stradins University, LV-1007 Riga, Latvia.
Latvian Biomedical Research and Study Centre, Ratsupites Str. 1-k1, LV-1067 Riga, Latvia.
Curr Issues Mol Biol. 2024 Mar 17;46(3):2553-2565. doi: 10.3390/cimb46030162.
The interplay of genetic, immune and environmental factors strongly contributes to the development of autoimmune thyroid disease (AITD), which can be classified as Graves' disease (GD) or Hashimoto thyroiditis (HT). One of the most studied exogenous factors in the pathogenesis of AITD is selenium, which, in the form of selenoproteins, strengthens the antioxidative defence system of thyroid cells against superoxide production. Furthermore, it modulates inflammatory cytokine release and autoantibody production. The aim of this study was to assess the associations of genetic factors with selenium levels in a cohort of adults with HT and GD and healthy controls from Latvia. A total of 148 GD patients, 102 HT patients and 2442 control participants were included in the study. The genotypes were determined using genome-wide genotyping; imputation was carried out using the TOPMed r2 imputation panel; and association analysis was performed with PLINK v1.90b7. We found three loci associated with GD (LSAMP, HNRNPA3P5, and NTN1) and one locus associated with HT (VAT1L); furthermore, one locus was associated with a serum selenium concentration > 80 µg/L (LINC01544/RNF152/PIGN). The detected associations could be attributed to population-specific effects or unknown stratification in our cohort, and further assessment of these results is required to explain the relationships of genetic traits with AITD and other phenotypes.
遗传、免疫和环境因素的相互作用在自身免疫性甲状腺疾病（AITD）的发展中起着重要作用，AITD可分为格雷夫斯病（GD）或桥本甲状腺炎（HT）。在AITD发病机制中研究最多的外源性因素之一是硒，硒以硒蛋白的形式增强甲状腺细胞的抗氧化防御系统，抵抗超氧化物的产生。此外，它还调节炎症细胞因子的释放和自身抗体的产生。本研究的目的是评估来自拉脱维亚的HT和GD成年患者队列以及健康对照中遗传因素与硒水平的关联。该研究共纳入了148名GD患者、102名HT患者和2442名对照参与者。使用全基因组基因分型确定基因型；使用TOPMed r2插补面板进行插补；并使用PLINK v1.90b7进行关联分析。我们发现了三个与GD相关的基因座（LSAMP、HNRNPA3P5和NTN1）和一个与HT相关的基因座（VAT1L）；此外，一个基因座与血清硒浓度>80μg/L相关（LINC01544/RNF152/PIGN）。检测到的关联可能归因于我们队列中的人群特异性效应或未知分层，需要对这些结果进行进一步评估，以解释遗传特征与AITD及其他表型之间的关系。
