Lack of an association between interleukin-6 -174G/C polymorphism and circulating interleukin-6 levels in normal population: a meta-analysis.

Interleukin-6 (IL-6) signaling may play a causal role in the development of coronary heart disease. However, the relationship between IL-6 genotypes and plasma levels of IL-6 appears to be complex. To help clarify the inconsistent findings, we conducted a meta-analysis of the published genetic association studies of the -174 G/C polymorphisms in the IL-6 gene and the circulating IL-6 levels in a normal population. In this meta-analysis, no significant association of IL-6 -174G/C polymorphism and circulating IL-6 levels in a normal population was observed. However, when compared among GG, GC, and CC genotypes, heterogeneity existed among the studies. Sensitivity analysis revealed that, the independent study by Shen et al. influenced the heterogeneity in the homozygous and heterozygous comparison. Although Shen et al.'s study was excluded, no significant association was observed between IL-6 -174G/C polymorphism and circulating IL-6 levels in a normal population [homozygous comparison (GG vs. CC): the pooled standard mean difference (SMD) was -0.01, 95% confidence interval (CI): -0.1-0.08; heterozygous comparison (GC vs. GG or CC): the pooled SMD (GG vs. GC) was -0.05, 95%CI: -0.11-0.01, and the pooled SMD (CC vs. GC) was 0.03, 95%CI: -0.03-0.1]. Under the dominant model, the pooled SMD was -0.05, 95%CI: -0.11-0.01). The meta-analysis provides evidence that the -174G/C polymorphism in the IL-6 gene is not significantly associated with circulating IL-6 levels in a normal population.