engleski

Genome-wide association analysis of food-specific antibodies in patients with Hashimoto's thyroiditis

The goal: Hashimoto's thyroiditis (HT) is influenced by both genetic and environmental factors. As diet has been already associated with HT, the goal of our study was to analyse genetic background behind increased immunological response to food antigens in HT patients. Materials and methods: We performed a genome-wide association analysis (GWAS) of 12 food-specific immunoglobulins G (IgG) that were measured in serum of 74 HT patients using microarray-based ELISA test and had concentrations above the reference range (≥ 30 U/ml). Two of these IgGs (for almond and plum) were previously found to be associated with HT aetiology/symptomatology. GWAS was performed using linear regression model adjusted for age and sex. Results: Our most significant associations were found for HT- associated almond and plum specific IgGs. Two genome-wide significant associations were found for almond specific IgG: rs1268150 located 34 kb from FOXO3 (P=4, 04×10-9) and rs7160273 inside INF2 (P=3, 32×10-8), and one suggestively associated variant with plum specific IgG: rs4870456 located 232 kb from IYD (P=2, 53×10-7). We identified four additional suggestively associated loci (P<10-6) with IgGs specific to pea, corn, wheat and sheep milk. Conclusion: FOXO3 functions as a trigger for apoptosis and interestingly, increased apoptosis of thyrocytes in one of the key features of thyroid tissue of HT patients. IYD encodes an enzyme that catalyses by- products of thyroid hormone production. Analysis of genetic background of food-specific IgGs revealed associations of genes that are relevant for thyroid function of HT patients, suggesting their role in HT manifestation

Hashimotov tireoiditis, genetics, food

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