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Review
. 2016 Jun;95(23):e3855.
doi: 10.1097/MD.0000000000003855.

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

Bing Li  1 , Yu Xiao, Dan Xing, Xin-Long Ma, Jun Liu
Affiliations
Review

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

Bing Li et al. Medicine (Baltimore). 2016 Jun.

Erratum in

  • Erratum: Medicine, Volume 95, Issue 23: Erratum.
    [No authors listed] [No authors listed] Medicine (Baltimore). 2016 Jul 18;95(28):e0916. doi: 10.1097/01.md.0000489580.04709.16. eCollection 2016 Jul. Medicine (Baltimore). 2016. PMID: 31265603 Free PMC article.

Abstract

Interleukin-6 (IL-6), as a pleiotropic cytokine, has been demonstrated to be closely associated with the pathogenisis of rheumatoid arthritis (RA). However, whether this association is causal or not remains unclear, because of the multifactorial role of IL-6 and related confounding factors. We aimed to evaluate the causal relevance between circulating IL-6 levels and the risk of RA through meta-analytical Mendelian randomization approach. IL-6 gene -174G/C variant was selected as an instrument in this Mendelian randomization meta-analysis. Article identification and data collection were conducted in duplicate and independently by 2 authors. The STATA software was used for data analysis. In total, 15 and 5 articles on the association of the -174G/C variant with RA risk and circulating IL-6 level, respectively, were included. The overall analysis showed that C allelic and GC+CC genotype were significantly with 1.59-fold (95% CI: 1.19-2.14) and 1.63-fold (95% CI: 1.17-2.26) increased risk of developing RA, respectively. Asian populations showed stronger association with 4.55-fold (95% CI: 1.62-12.75), 1.84-fold (95% CI: 1.13-2.99), and 4.69-fold (95% CI: 1.68-13.14) increased RA risk in carriers of -174C allelic, CC, and GC+CC genotype, respectively. Carriers of GC+CC genotype showed significant reduction in the circulating IL-6 level compared with GG carriers (WMD = -0.77; 95% CI: -1.16 to -0.38; P = 0.000) in overall populations. Mendelian randomization presented 6% and 22% increased risk of RA with 0.1 pg/mL reduction of circulating IL-6 level in overall and Asian populations, respectively. This Mendelian randomization meta-analysis demonstrated that the long-term genetically reduced circulating IL-6 level might be causally related to a higher risk of RA, especially in Asian populations.

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Conflict of interest statement

The authors have no conflicts of interest to disclose.

Figures

Figure 1
Figure 1
Flow diagram of the search strategy and study selection.
Figure 2
Figure 2
Overall comparisons of interleukin-6 (IL-6) -174 gene C versus G (A) and genotype GC+CC versus GG (B) in association with RA risk.
Figure 3
Figure 3
Begg funnel plot analysis to detect publication bias for the comparisons of interleukin-6 (IL-6) -174 gene C versus G (A) and genotype GC+CC versus GG (B).
Figure 4
Figure 4
Meta-analysis for the association of the IL-6 -174G/C variants and circulating IL-6 level under the dominant model (GC+CC vs GG).
See this image and copyright information in PMC

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