Impact of CTLA-4 gene polymorphism on organ-specific antibody levels in patients with autoimmune thyroiditis in the Azerbaijani population

Abstract

BACKGROUND: The risk of developing immune tolerance to autoantigens in autoimmune thyroiditis is largely associated with mutations in the CTLA-4 gene, whose product negatively regulates T-cell activity.

AIM: The study aimed to investigate the +49A/G (rs231775) polymorphism of the CTLA-4 gene in patients with autoimmune thyroiditis within a sample of the Azerbaijani population and assess the impact of allele and genotype frequencies on anti-thyroperoxidase and anti-thyroglobulin antibodies.

METHODS: A study was conducted from 2021 to 2023 and included 170 patients with autoimmune thyroiditis (study group) and 65 individuals without thyroid pathology or other autoimmune diseases (control group). The sex and age of the groups were comparable. Autoimmune thyroiditis was diagnosed on the basis of medical history, assessment of thyroid status, thyroid ultrasound, and the presence of organ-specific antibodies. The results of routine thyroid function tests in the control group were within the normal range. Genotyping of the +49A/G (rs231775) polymorphism was performed by polymerase chain reaction followed by restriction fragment length polymorphism analysis using PspEI endonuclease. Quantitative variables were presented as the median (Me) and interquartile range (IQR; 25th percentile, 75th percentile). Hardy–Weinberg equilibrium for genotype frequencies was assessed using the χ² test.

RESULTS: The study revealed a statistically significant increase in the frequency of the G allele (48%) compared with the control group (33.8%; p = 0.039, χ² = 4.27, odds ratio [OR] = 1.865, 95% confidence interval [CI]: 1.028–3.382) and a decrease in the frequency of the A allele (51.2%) relative to the control group (66.1%; p = 0.0389, χ² = 4.27, OR = 0.536, 95% CI: 0.296–0.973). Anti-thyroglobulin antibody titers exceeding 100 IU/mL 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 55.6% of patients carrying the G allele (p = 0.0012, χ² = 10.43, OR = 0.360, 95% CI: 0.192–0.674). Anti-thyroperoxidase antibody levels ≥100 IU/mL were found in 22.7% of individuals with the GG genotype (p = 0.030) and 50.0% of those carrying the G allele (p = 0.048).

CONCLUSION: Elevated anti-thyroperoxidase and anti-thyroglobulin antibody titers were identified in individuals carrying the G allele and the homozygous GG genotype of the +49A/G polymorphism of the CTLA-4 gene in the Azerbaijani population.

Keywords

autoimmune thyroiditis / alleles / genotype / polymorphism / CTLA-4 gene / CTLA-4 gene product / autoantibodies

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