GPX1 Pro198Leu (rs1050450) genotype, oxidative stress, and thyroid functional status in autoimmune thyroiditis: a cross-sectional study

Autoimmune thyroiditis (AIT) is a common autoimmune endocrine disorder in which redox imbalance may accompany thyroid dysfunction. Glutathione peroxidase-1 (GPX1) is a predominantly intracellular antioxidant enzyme that limits hydrogen peroxide and lipid hydroperoxide accumulation. The functional GPX1 Pro198Leu (rs1050450) variant has been linked to altered antioxidant capacity, but its relationship with thyroid functional status in AIT remains uncertain. To evaluate GPX1 Pro198Leu (rs1050450) genotype distribution and oxidative-stress biomarkers across thyroid functional states in patients with autoimmune thyroiditis, without inferring disease susceptibility in the absence of genotyped healthy controls. This cross-sectional observational study included 72 adults with autoimmune thyroiditis, classified as euthyroid (n = 45) or hypothyroid (n = 27), and 20 apparently healthy volunteers used only as a biochemical reference group. Thyroid function, thyroid autoantibodies, glutathione peroxidase (GPX) activity, and malondialdehyde (MDA) were assessed. GPX1 rs1050450 genotyping was performed in the AIT cohort. Genotype and allele distributions were compared between euthyroid and hypothyroid AIT groups; Hardy-Weinberg equilibrium and genotype-stratified oxidative-stress analyses were performed. Healthy controls were not included in genetic association analyses. GPX activity was lower and MDA higher across healthy controls, euthyroid AIT, and hypothyroid AIT (both P < 0.001). Genotype frequencies did not differ significantly between euthyroid and hypothyroid AIT (overall χ²=3.80, P = 0.148). No individual allele or genotype showed a statistically significant association with hypothyroid status; for C/C, OR = 4.00 (95% CI 0.90-18.22; P = 0.07), indicating substantial imprecision. Across the three genotype groups, GPX activity differed by one-way ANOVA (P = 0.017) and MDA differed by one-way ANOVA (P = 0.0048). The euthyroid AIT subgroup deviated from Hardy-Weinberg equilibrium (χ²=6.922, P = 0.0085; FIS = + 0.392), whereas the hypothyroid subgroup did not (χ²=0.0064, P = 0.936; FIS=-0.015). In this small cross-sectional AIT cohort, oxidative-stress biomarkers differed by thyroid functional status and by GPX1 rs1050450 genotype group, but no statistically significant association between rs1050450 and hypothyroid status was demonstrated. Because healthy controls were not genotyped, the study cannot assess association with AIT susceptibility. The small sample, single-center design, Hardy-Weinberg disequilibrium in one subgroup, and unmeasured treatment and smoking-related confounding require cautious interpretation. Larger studies with population-matched genotyped controls and prospectively characterized covariates are needed. Not applicable.