Rheumatoid arthritis (RA) is a persistent inflammatory autoimmune disease that impacts joints and leads to gradual deterioration. Cytokines like IL-17 and IL-21 are associated with the etiology of rheumatoid arthritis due to their involvement in fostering inflammation and autoimmunity. This study investigated the association between single- nucleotide polymorphisms (SNPs) in IL-17F (rs2397084 and rs11465553) and IL-21 (rs2221903) genes and susceptibility to rheumatoid arthritis in an Iraqi cohort. The case-control study included 90 participants (50 RA patients and 40 healthy controls) from Ramadi, Al-Anbar, between November 2023 and January 2024. Genomic DNA was extracted from blood samples, and SNP genotyping was conducted using AS-PCR and ARMS-PCR techniques. Results showed a significant association between the C allele of IL-17F rs2397084 and RA susceptibility (frequency: 0.31 in patients vs. 0.16 in controls, 𝜒2 = 5.235, 𝑝 = 0.022), with genotype distributions of T/T (0.48), T/C (0.42), and C/C (0.10) in patients compared with 0.72, 0.22, and 0.05 in controls (p=0.063). The dominant model (T/C + C/C) indicated increased risk (OR=7.71, 95% CI: 1.43-41.53, p=0.008). For rs11465553, the A allele was more frequent in patients (0.38 vs. 0.06, 𝜒2 = 24.641, 𝑝 < 0.001), with genotype distributions of A/A (0.30), G/A (0.16), and G/G (0.54) in patients compared with 0.02, 0.08, and 0.90 in controls (𝜒2 = 14.881, 𝑝 = 0.001). The dominant (OR=6.28, 95% CI: 1.43- 27.60, p=0.0097) and recessive models (OR=11.64, 95% CI: 1.21-111.53, p=0.0095) confirmed this association. For IL-21 rs2221903, the T allele was more prevalent (71 in patients vs. 44 in controls,𝜒2 = 6.378, 𝑝 = 0.012), with genotype distributions of T/T (n=23), T/C (n=25), and C/C (n=2) in patients compared with T/C (n=28), C/C (n=4), and T/T (n=8) in controls (𝜒2 = 46.586, 𝑝 < 0.001). However, genetic model analysis showed no significant associations (e.g., dominant model OR=0.30, p=0.095). Deviations from Hardy-Weinberg equilibrium were observed for rs11465553 in patients (p<0.0001) and rs2221903 in controls (p=0.023), possibly reflecting disease effects or sample size limitations. These findings suggest that IL-17 and IL-21 genetic variations may contribute to RA susceptibility in the Iraqi population. Further studies in larger, multiethnic cohorts are warranted to confirm these associations and elucidate underlying mechanisms.
Masser et al. (Wed,) studied this question.