The Impact of the Taq-I (rs731236) Genetic Variant in the Vitamin D Receptor on the Risk and Severity of Rheumatoid Arthritis in Syrian Patients

Background and Objective: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by Persistent joint inflammation, systemic complications, and increased mortality rates. Vitamin D receptors (VDR) Play a regulatory role in the immune system, and their genetic variations are believed to influence susceptibility to RA. This study aimed to investigate the association between the Taq-I (rs731236) single nucleotide Polymorphism (SNP) in the VDR gene and the risk of developing RA, as well as to assess the impact of this variant on disease activity and serum levels of vitamin D in a Syrian cohort.

Materials and Methods: This case-control study was conducted at Al-Mouwasat and Al-Watani University Hospitals in Damascus between March and June 2023. It included 100 RA Patients and 100 age- and sex-matched healthy controls. Serum concentrations of 25(OH)D were measured using electrochemiluminescence immunoassay. Disease activity was assessed using the DAS28-CRP index. Genotyping of the Taq-I variant was Performed by PCR followed by Sanger sequencing. Statistical analyses were Performed using SPSS version 26.

Results: RA Patients showed a statistically significant reduction in mean serum vitamin D levels compared to controls (22.38 ± 15.80 vs. 27.56 ± 13.04 ng/mL, P= 0.036), with a higher frequency of vitamin D deficiency/insufficiency (50% vs. 35%). A significant difference in allele frequencies of the Taq-I-I variant was found between patients and controls (P= 0.001). The G allele was associated with an increased risk of RA (odds ratio [OR] = 2.00, P= 0.001). Additionally, the homozygous AA genotype was linked to higher disease severity (DAS28 ≥ 5.1).

Conclusions: The Taq-I (rs731236) variant in the VDR gene is associated with increased risk and severity of RA in the studied Syrian sample. The findings suggest the need for larger-scale studies to confirm this association and explore underlying mechanisms.