The Association Between Interleukin-6 Promoter Polymorphisms and Rheumatoid Arthritis by Ethnicity: A Meta-analysis of 33 Studies

Objective: We performed a meta-analysis to determine the effect Interleukin-6 (IL-6) promoter polymorphism (-174 G>C, -572 G>C, and -597 G>A) have on the development rheumatoid arthritis (RA) by ethnicity.

Material And Methods: PubMed, EBSCO, LILACS, and Scopus databases were searched for studies exploring the association between any IL6 polymorphisms and RA until November 2018. Genotype distributions were extracted and, depending on the level heterogeneity, determined by the ψ-based Q test and the Inconsistency Index (I), fixed-effects or random-effects models were used to calculate pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) for the heterozygous, homozygous, dominant, recessive, and allelic genetic models.

Results: From 708 identified publications, 33 were used in this analysis. For the -174 polymorphism, Asians (OR=7.57, 95%CI: 2.28-25.14, OR=5.84, 95%CI: 2.06-16.56, OR=7.21, 95%CI: 2.30-22.63, OR=5.04, 95%CI: 1.78-14.28, OR=6.60, 95%CI: 2.26-19.28, p<.05) and Middle East countries (OR=2.30, 95%CI: 1.10-4.81, OR=2.27, 95%CI: 1.22-4.22, OR=2.29, 95%CI: 1.24-4.23, p<.05) were associated with a significant risk of developing RA. Whereas, for Latinos, the C-allele was associated with a benefit (OR=0.26, 95%CI: .08-.82, OR=.25, 95%CI: .08-.80, p<.05). For the -572 polymorphism, Asians demonstrated a significant association for the homozygous and recessive genetic models (8 studies, OR=1.56, 95%CI: 1.16-2.09, OR=1.63, 95%CI: 1.08-2.45, p<.05). For the -597 polymorphism, no association was observed.

Conclusions: Here, the -174 G>C polymorphism increased the risk of developing RA in Asians and Middle East populations. Interestingly, for Latinos, the polymorphism was associated with a benefit. For the -572 polymorphism, only the Asian population showed an increased risk of developing RA for the CC genotype.