RESUMO
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.
RESUMO
Autoimmune thyroid disease (AITD), including Graves' disease (GD) or Hashimoto's thyroiditis (HT), occurs due to genetic susceptibility and environmental factors, among which the role of stressful events remains controversial. This study investigated the relationship between the number and impact of stressful life events in AITD patients with selenium status, and the Th1/Th2/Th17 immune response. The study population included three groups: HT (n = 47), GD (n = 13), and a control group (n = 49). Thyroid function parameters, autoantibody levels, and the plasma levels of cytokines, selenium, selenoprotein P (SeP), and glutathione peroxidase 3 (GPx) activity were measured. Participants filled out the Life Experiences Survey. No significant differences in the number of stressful life events were found among the patients with HT, GD, and the controls. A higher (median (interquartile range)) negative stress level (8 (4-12)) than a positive stress level (3 (1-9)) was found in the HT group. The HT group showed a correlation between SeP and the positive stress level: rs = -0.296, p = 0.048, and the GD group between GPx and the negative stress level (rs = -0.702, p = 0.011). Significant positive correlations between thyroid peroxidase antibody level and the total number of major life events (p = 0.023), the number of major life events in the last 7-12 months, and the number of major life events with no impact and a negative stress level were found. We suggest that the measurements of Th2-related cytokines and selenoproteins could be used as biomarkers for the development of AITD in cases where stress is considered a component cause of the pathogenic mechanism of the disease.
