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. 2024 Mar 17;46(3):2553-2565.
doi: 10.3390/cimb46030162.

Genetic and Environmental Factors in Autoimmune Thyroid Disease: Exploring Associations with Selenium Levels and Novel Loci in a Latvian Cohort

Sabine Upmale-Engela  1 , Ieva Vaivode  1 , Raitis Peculis  2 , Helena Litvina  2 , Tatjana Zake  1 , Andrejs Skesters  3 , Deniss Gogins  1 , Vita Rovite  2 , Ilze Konrade  1   4
Affiliations

Genetic and Environmental Factors in Autoimmune Thyroid Disease: Exploring Associations with Selenium Levels and Novel Loci in a Latvian Cohort

Sabine Upmale-Engela et al. Curr Issues Mol Biol. .

Abstract

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.

Keywords: autoimmune thyroid diseases; genome-wide association; selenium.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Manhattan plots showing the associations between SNPs and (a) Graves’ disease and (b) Hashimoto thyroiditis.
Figure 2
Figure 2
Regional association plots of (a) CEP128 and TSHR and (b) HLA-DQA1.
Figure 3
Figure 3
Manhattan plot showing the association between the SNP rs6567243 and a serum selenium concentration > 80 µg/L.
Figure 4
Figure 4
Detailed regional view of the leading associated SNP rs6567243.
See this image and copyright information in PMC

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