Impact of IL6 and IL18 Promoter Polymorphisms on Circulating Cytokine Levels, Gene Expression, and Susceptibility to Rheumatoid Arthritis

Our study examined the impact of IL6 −174 G/C (rs1800795) and IL18 −607 C/A (rs1946518) promoter polymorphisms on susceptibility to rheumatoid arthritis (RA) and protein/mRNA levels. RA patients had significantly higher serum IL-6 and IL-18 levels than controls; healthy men had higher IL-18 than women (p < 0.001). Conversely, IL6 mRNA expression was lower in RA patients than controls (p = 0.037). No link was found between rs1800795 and RA susceptibility; however, the CC genotype was less frequent among RA patients than controls, suggesting potential protection (OR = 0.55). Also, the −174 G allele was probably associated with RF positivity (OR = 1.4). In RA patients, no significant association was detected between the −174 G/C polymorphism and either IL6 mRNA expression or circulating IL-6 levels. Among healthy individuals, carriers of the GG genotype showed higher IL6 mRNA expression (p = 0.024). No association was observed between rs1946518 and RA risk or clinical features, or between systemic IL18 mRNA, IL-18 levels, and rs1946518 genotypes in RA patients. In summary, rs1800795 showed borderline association with disease risk and autoantibody presence, whereas rs1946518 was not associated with RA susceptibility, cytokine levels, or key clinical characteristics in our cohort.