Relationship between CTLA4, TNF-α and PTPN22 gene polymorphism and the serum levels of antithyroglobulin and antiperoxidase antibodies in autoimmune thyroiditis

Abstract

Autoimmune thyroiditis (AIT) is a chronic inflammatory that involves hyperactivation of the immune system against the thyroid gland, recognizing it as "nonself”. The aim of this research was to identify the relationships between genetic polymorphism in CTLA4, TNF-α and PTPN22 genes and the manifestation of AIT and levels of antithyroglobulin antibody (anti-TG Ab) and thyroid peroxidase antibody (anti-TPO Ab). The study was conducted during 2014–2020 and included 64 men and 106 women aged between 18 and 64 years with AIT. The control group consisted of 65 people (26 men, 39 women, aged between 20 and 65 years) without any thyroid pathologies or other autoimmune diseases. For molecular genetic analysis, real-time quantitative RT-PCR was used with fluorescently labeled FAM probes on a detection system CFX96 (BioRad). The results demonstrated that patients with the GG genotype and the G allele of the +49A/G polymorphism in the CTLA4 gene have significantly higher titers of anti-TG Ab. High titers of anti-TG Ab were detected in 22.4% of patients with the GG genotype (p = 0.005, χ2 = 7.86, OR = 0.237, 95% CI = 0.088–0.635), and in 55.6% of patients with the G allele (p = 0.0012, χ2 = 10.43, OR = 0.360, 95%, СI = 0.192–0.674). At the same time, the A allele of the +49A/G polymorphism is significantly more common in patients with normal anti-TG Ab values—in 68.1% of individuals (p = 0.0012, χ2 = 10.43, OR= 2.78, 95%, CI = 1.484–5.207). The results of the study indicate the prognostic significance of the G allele and the GG genotype of the +49A/G polymorphism of the CTLA4 gene predicting the probability of occurrence of anti-TG and anti-TPO antibodies.