The Association between Interleukin-6 Gene Polymorphisms and Risk of Systemic Lupus Erythematosus: A Meta-analysis with Trial Sequential Analysis

ABSTRACT

Background

Molecular epidemiological studies have sought associations between interleukin-6 (IL-6) polymorphisms and the risk of systemic lupus erythematosus (SLE); however, the results are controversial. Therefore, we conducted a meta-analysis with trial sequential analysis to evaluate a more accurate estimation of the associations.

Methods

Published literatures reporting the relationships of two IL-6 polymorphisms (G-174C and G-572C) and SLE risk were retrieved from electronic databases such as PubMed and EMBASE. The most appropriate genetic model was chosen for each polymorphism. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Trial sequential analysis (TSA) was introduced to assess the information size and the positive results.

Results

With 17 studies (2780 cases and 3100 controls) included, a dominant association (CC+GC vs. GG) was suggested for G-174C polymorphism, and compared with the GG genotype, the CC+GC genotype of G-174C was associated with a decreased SLE risk (OR = 0.71; 95% CI = 0.56–0.88, P =.02). No association was found for G-572C under all genetic models (e.g. OR and 95%CI for CC+GC vs. GG: 0.89, 0.73–1.08, P =.22). Subgroup analyses indicated that SLE risk decreased in G-174C polymorphism by subgroups of Caucasian population, publications after 2010, studies with high quality, and studies complied with Hardy–Weinberg equilibrium (HWE). TSA suggested that the sample sizes used for G-572C were insufficient.

Conclusion

We found that the minor allele C of IL6G-174C polymorphism is a protective factor in SLE. Further studies with a larger sample size are needed to confirm the null association for G-572C.

KEYWORDS:

• Interleukin-6
• meta-analysis
• polymorphisms
• systemic lupus erythematosus
• trial sequential analysis

Disclosure statement

The authors declare that there was no conflict of interest.

SUPPLEMENTAL DATA

Supplemental data for this article can be accessed on the publisher’s website.

Additional information

Funding

This work was supported in part by the National Natural Science Foundation of China [Grant numbers: 81602853].