Circulating interleukin-6 and rheumatoid arthritis: A Mendelian randomization meta-analysis

Area of Science:

• Immunology
• Genetics
• Rheumatology

Background:

• Interleukin-6 (IL-6) is a cytokine implicated in rheumatoid arthritis (RA) pathogenesis.
• The causal relationship between IL-6 levels and RA risk remains unclear due to confounding factors.

Purpose of the Study:

• To investigate the causal relevance between circulating IL-6 levels and RA risk using a Mendelian randomization meta-analysis.
• To evaluate the association between the IL-6 gene -174G/C variant and RA risk.

Main Methods:

• A Mendelian randomization meta-analysis approach was employed.
• Data from 15 articles on the IL-6 -174G/C variant and RA risk, and 5 articles on IL-6 levels were analyzed.
• STATA software was used for statistical analysis.

Main Results:

• The C allele and GC+CC genotype of the IL-6 -174G/C variant were associated with increased RA risk (1.59-fold and 1.63-fold, respectively).
• Asian populations showed a stronger association, with increased RA risk for carriers of the -174C allele, CC, and GC+CC genotypes.
• Carriers of the GC+CC genotype had reduced circulating IL-6 levels compared to GG carriers (WMD = -0.77).

Conclusions:

• Genetically reduced circulating IL-6 levels may be causally linked to a higher risk of developing RA.
• This causal association appears more pronounced in Asian populations.
• The findings support a potential role for IL-6 in RA etiology.