Genetic copy number variation of TLR7, T-bet, IL12B, and FcγRIIIB in Egyptian ankylosing spondylitis patients

Background: Ankylosing spondylitis (AS) is a polygenic disorder. Copy number variations (CNVs) alter the expression of TLR7, T-bet, IL-12B, and FcγRIIIB genes, contributing to AS development via their immune system roles. Objective: The current study aimed to assess the correlation between AS susceptibility and CNVs of TLR7, T-bet, IL12B, and FcγRIIIB, as well as their influence on disease activity. Methods: The study involved 42 healthy controls and 72 patients with AS, recruited from the Rheumatology and Rehabilitation clinic of Zagazig University Hospitals, Zagazig, Egypt, from 01 November 2023 to 30 October 2024. Sociodemographic, clinical data and blood samples were collected from all participants. Copy number estimations for TLR7, T-bet, IL12B, and FcγRIIIB genes were performed using SYBR Green real-time polymerase chain reaction. Results: Of 72 cases aged 19 to 52 years, 47 (65.2%) were men and 25 (34.8%) were women. Controls included 42 participants aged 27 to 55 years, 22 (52.4%) men and 20 (47.6%) women. Higher IL12b and FcγRIIIB gene copy numbers were significantly associated with a higher risk of AS (p = 0.001, odds ratio [OR]: 3.8, 95% confidence interval [CI]: 1.7–8.07, and p < 0.001, OR: 5.5, 95% CI: 2.31–13.08, respectively). While T-bet and TLR7 gene CNVs showed no significant association with AS risk. No significant association was observed between the studied CNVs and AS activity. Conclusion: High copy numbers of IL12B and FcγRIIIB genes may be associated with increased AS risk. However, no significant correlation was found between AS risk and TLR7 or T-bet CNVs. What this study adds: The findings of this study revealed that genetic copy number variations may contribute to the risk of AS.