Longitudinal Associations Between TPO Gene Variants and TPOAb Seroconversion in a Population Based Study: Tehran Thyroid Study (TTS)

Abstract

Background: Autoimmune thyroid diseases are among the most common autoimmune diseases in the world. They are usually accompanied by the presence of anti-thyroid antibodies as the early predictive marker. Genetic determinants of the susceptibility to develop thyroid antibodies are still poorly understood. This study aimed to investigate the relation between thyroid peroxidase (TPO) gene variants (53 SNPs) and positive TPOAb and also to evaluate the effect of some environmental factors on changes from negative to positive TPOAb (Seroconversion). Methods: Participants from the Tehran Thyroid Study (TTS) in phases 1 and 2 (N=5317, ≥ 20 years) were evaluated for the positive TPOAb and its relationship with 53 SNPs from TPO gene (a cross-sectional approach). At the second stage of the study (a longitudinal approach), negative TPOAb participants (control group, N= 4815) were followed up for about 5.5 (5.54±1.62) years until they have had positive results for TPOAb (“TPOAb seroconversion”). The association between TPO gene polymorphisms and TPOAb seroconversion was evaluated using logistic regression analysis and SKAT package (sequence kernel association test). Results: In cross-sectional analyses, 17 SNPs were associated with TPOAb positivity (521 positive TPOAb participants) after the adjustment for age, sex, body mass index (BMI), smoking, the number of parity and oral contraceptive consumption (P <0.05). In longitudinal analyses, there was an association between TPOAb seroconversion and four SNPs before, and three SNPs after adjustment (P <0.05). Conclusions: TPOAb seroconversion could be affected by some thyroid peroxidase gene variants.