ECE2024 Poster Presentations Thyroid (58 abstracts)
Genetic and environmental factors in autoimmune thyroid disease: exploring the associations with selenium levels and novel genetic loci in a latvian cohort
Sabine Upmale-Engela 1 , 2 , Ieva Kalere 3 , Raitis Pečulis 4 , Raimonds Rescenko 4 , Helena Litvina 4 , Tatjana Zake 5 , Andrejs Skesters 6 , Deniss Gogins 1 , Vita Rovite 4 & Ilze Konrade & 5
1Riga Stradins University, Faculty of Residency, Rīga, Latvia; 2Riga East Clinical University Hospital, Department of Endocrinology, Rīga, Latvia; 3Riga Stradins University, Daculty of Doctoral Studies, Rīga, Latvia; 4Latvian Biomedical Research and Study centre, Rīga, Latvia; 5Riga Stradins University, Department of Internal Diseases, Rīga, Latvia; 6Riga Stradins University, Laboratory of Biochemistry, Rīga, Latvia
Background: The interplay of genetic, immune and environmental factors strongly contributes to the development of autoimmune thyroid disease (AITD) in the form of Graves’ disease (GD) and 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.
Purpose: The aim of this study was to assess the association of genetic factors with selenium levels in an adult cohort with HT and GD, and healthy controls from Latvia.
Materials and Methods: A total of 2692 subjects were included in a cross-sectional study. They were divided into 3 groups:GD(n=148), HT(n=102), and a control group(n=2442). Diagnosis of AITD was based on laboratory evaluation. In addition, serum selenium levels were measured and selenium intake score was assessed. The genotypes were determined using genome wide genotyping, imputation was carried out using TOPMed r2 imputation panel, and association analysis was performed with PLINK2.9.
Results: Out of 2692 participants 1684 were female (62.6%), 1008 – male (37.4%). Mean age was 54.3 years (SD 14.0) in the Control Group, 48.4 (SD 15.6) in GD, and 48.3 (SD 15.6) in HT patients. Mean selenium level was 84.4μg/L (SD 31.3), 69.3 μg/L (SD 17.1), and 83.4 μg/L (SD 27.0) in the respective groups. The overall cohort selenium level was below the reference levels(80-125 μg/L) for 62% of the participants (49% controls, 77% GD and 54% HT), with GD patients having significantly lower levels. Additionally, we found three loci associated with GD (LSAMP, HNRNPA3P5, NTN1) on chromosomes 3, 13, 17, respectively, and one locus associated with HT (VAT1L) on chromosome 16. Most of these lead SNPs of significantly associated characteristics have low population minor allele frequencies (<5%) and a fairly large effect (OR>3). Furthermore, one locus rs6567243 was associated with serum selenium >80 µg/L (LINC01544/RNF152/PIGN) on chromosome 18 [OR (95% CI) = 2.46 (1.76-3.43); P<0.001]. This SNP has a high minor allele frequency (54.8%) in a Non-Finnish European reference population.
Conclusion: The associations with the novel loci could be attributed to population-specific effects or unknown stratification in our cohort, and further assessment of these hits are required to explain the relation of genetic traits with studied AITD and other phenotypes. This study was supported by the Latvian Council of Science(Grant No:lzp-2018/2-0059).
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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