IL-4 polymorphisms (rs2227284, rs2243267, and rs2243270) are associated with reduced risk of rheumatoid arthritis.

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease, and understanding its genetic and molecular basis is crucial for early diagnosis, treatment, and prevention.

Objective: This study aims to explore the association between IL-4 polymorphisms (rs2227284, rs2243267, rs2243270, and rs2243283) and RA risk.

Methods: The four IL-4 polymorphisms were genotyped in 493 RA patients and 493 healthy controls using Agena MassARRAY. Logistic regression analysis calculated odds ratio (OR) and 95% confidence interval (CI) to estimate the relationship between IL-4 polymorphisms and RA risk.

Results: Overall analysis revealed that rs2243267 (GG vs. CC: OR = 0.26, FDR-p = .032; Recessive: OR = 0.27, FDR-p = .048) and rs2243270 (AA vs. GG: OR = 0.26, FDR-p = .024; Recessive: OR = 0.27, FDR-p = .024) were associated with a decreased risk of RA. Stratified analysis indicated that rs2243267 and rs2243270 were correlated with reduced RA risk in female, smoking, BMI <24, and drinking population; rs2227284 was associated with a decreased RA risk in BMI <24 and drinking population. Moreover, rs2243267 and rs2243270 were significantly associated with reduced ACPA positivity.

Conclusions: Our findings suggest that IL-4 polymorphisms (rs2227284, rs2243267, and rs2243270) act as protective factors for RA in the Chinese Han population.