Association of IL-6 rs1800795 (− 174G > C) polymorphism with depression risk: a comprehensive meta-analysis

Depression is a global public health concern with a steadily increasing prevalence. Previous studies examining the association between interleukin-6 (IL-6) gene polymorphisms and depression have produced inconsistent findings. Therefore, we conducted a meta-analysis to clarify the association between IL-6 gene polymorphisms and susceptibility to depression. From eight eligible articles identified, seven studies providing data for the rs1800795 variant were included in the quantitative synthesis. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the genetic association under allelic, dominant, recessive, homozygous, and heterozygous genetic models. The meta-analysis revealed no significant association between the IL-6 rs1800795 polymorphism and susceptibility to depression under the allelic, dominant, recessive, homozygous, and heterozygous genetic models (G vs. C, OR = 1.05, 95%CI: 0.83–1.32, P = 0.70; GG + CG vs. CC, OR = 1.10, 95%CI: 0.69–1.75, P = 0.68; GG vs. CC + CG, OR = 1.11, 95%CI: 0.87–1.43, P = 0.40; GG vs. CC, OR = 1.24, 95%CI: 0.79–1.94, P = 0.35; CG vs. CC, OR = 1.04, 95%CI: 0.65–1.66, P = 0.87). Subgroup analyses stratified by control source and participants’ physical condition also revealed no significant associations under any genetic model. Although no direct association was found, our findings suggest that IL-6 rs1800795 does not confer categorical risk in isolation. Future research should prioritize gene-environment interactions rather than single-locus effects to clarify its role in depression pathogenesis.