Inflammatory factor Interleukin-6 and its correlation with rheumatoid arthritis: A meta-analysis

Xiaojuan Hao; Huani Zhao; Linhui Zhu; Zhiteng Li; Jing Yang; Qian Bai

doi:10.1016/j.heliyon.2024.e39472

Inflammatory factor Interleukin-6 and its correlation with rheumatoid arthritis: A meta-analysis

Heliyon. 2024 Oct 17;10(23):e39472. doi: 10.1016/j.heliyon.2024.e39472. eCollection 2024 Dec 15.

Authors

Xiaojuan Hao¹, Huani Zhao², Linhui Zhu², Zhiteng Li¹, Jing Yang², Qian Bai¹

Affiliations

¹ Rheumatology and Immunology Department, Third Ward, The Fifth Hospital of Xi'an City, Xi'an, 710082, China.
² Rheumatology and Immunology Department, Second Ward, The Fifth Hospital of Xi'an City, Xi'an, 710082, China.

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 I² 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.

Keywords: Correlation; Genetic polymorphism; IL-6; Meta-analysis; Rheumatoid arthritis.