Abstract
INTRODUCTION: at present, there are inconsistent research findings regarding the precise relationship between IL-6 gene polymorphisms (GPMs) and rheumatoid arthritis (RA). This work employed meta-analysis (MA) methodology to systematically evaluate the correlation between IL-6 GPMs and susceptibility to RA. MATERIAL AND METHODS: this study comprehensively searched multiple databases from inception to March 31, 2024. The search utilized keywords including "IL-6," "Interleukin-6," "Cytokines," "Autoimmune diseases," "Arthritis," "rheumatoid arthritis," "Inflammation," "genetic polymorphism," and "genetic variation." Included studies focused on patients diagnosed with rheumatoid arthritis (RA), with healthy individuals or those without RA-related diseases as controls. The study designs encompassed cohort studies and case-control studies. Genetic frequency distributions of IL-6 gene rs1800795 (G-174C), rs1800796 (G-572C), and rs1800797 (G-597A) polymorphic sites were statistically analyzed. Quality of included studies was assessed. The preliminary assessment of literature heterogeneity was conducted. Quantitative assessment of heterogeneity results was performed using the I(2) statistic in RevMan5.3. Publication bias (PB) assessment was conducted. RESULT: the study included a total of 21 articles, comprising 9772 participants, with 4679 cases diagnosed with RA and 5093 individuals in the control (CT) group. The IL-6 gene allelic model (G vs C) exhibited a notable association with RA [OR = 0.66, 95%CI: 0.51-0.87, Z = 3.02, P = 0.003]. In Southeast Asian populations, IL-6 gene rs1800795 (G-174C) genotype (CC) demonstrated a considerable correlation with RA [OR = 15.23, 95%CI: 3.53-65.67, P = 0.00003]. IL-6 gene rs1800795 (G-174C) genotype (CG) was associated with RA [OR = 1.54, 95%CI: 1.10-2.17, Z = 2.48, P = 0.01], with only the Asian population showing an observable correlation [OR = 6.55, 95%CI: 1.28-33.45, P = 0.02]. Additionally, IL-6 rs1800795 (G-174C) genotype (GG) was associated with RA [OR = 0.66, 95%CI: 0.49-0.91, Z = 2.55, P = 0.01], with notable associations observed in the Asian [OR = 0.17, 95%CI: 0.03-0.83, P = 0.03] and mixed populations [OR = 1.29, 95%CI: 1.011.65, P = 0.04]. No correlation was found between rs1800796 (G-572C) and rs1800797 (G-597A) GPMs and RA (P > 0.05). CONCLUSION: IL-6 gene rs1800795 (G-174C) allelic model and genotypes (CC, CG, GG) were all associated with susceptibility to RA, with the G allele model being susceptible in Southeast Asian populations, and genotypes (CG and GG) being susceptible in Asian populations. However, there was neglectable correlation between rs1800796 (G-572C) and rs1800797 (G-597A) GPMs and susceptibility to RA.