The association between interleukin-6 gene polymorphisms and intracranial aneurysms: a meta-analysis

Interleukin-6 (IL-6) is an important proinflammatory cytokine, and some studies have demonstrated that IL-6 promoter polymorphisms (-174G/C and -572G/C) may be associated with intracranial aneurysms. A meta-analysis based on the evidence currently available from the literature was conducted to make a more precise estimation of this relationship.

Electronic databases (the National Library of Medline and Embase databases) were searched before June 2013. Odds ratio (OR) and 95% confidence interval (CI) were calculated in fixed- or random-effects models when appropriate. Subgroup analyses were performed by race. This meta-analysis included six case-control studies, which included 1188 intracranial aneurysms cases and 4099 controls.

The combined results based on all studies showed that intracranial aneurysms cases had a significantly lower frequency of -572CC [OR (Recessive model) = 0.47, 95% CI = 0.36, 0.60, P < 0.001; OR (Codominant model) = 0.29, 95% CI = 0.20, 0.44, P < 0.001], -572GC [OR (Codominant model) = 0.73, 95% CI = 0.55, 0.98, P = 0.04] and -174CC [OR (Recessive model) = 0.73, 95% CI = 0.54, 0.98, P = 0.03; OR (Codominant model) = 0.70, 95% CI = 0.51, 0.97, P = 0.03] genotype. In the subgroup analysis by race, we found that (1) intracranial aneurysms cases had a significantly lower frequency of -572CC [OR (Recessive model) = 0.41, 95% CI = 0.32, 0.53, P < 0.001; OR (Codominant model) = 0.18, 95% CI = 0.12, 0.29, P < 0.001] and -572GC [OR (Codominant model) = 0.61, 95% CI = 0.42, 0.88, P = 0.009] genotype in Asians; (2) intracranial aneurysms cases had a significantly higher frequency of -572CC [OR (Recessive model) = 4.41, 95% CI = 1.35, 14.36, P = 0.01; OR (Codominant model) = 4.41, 95% CI = 1.35, 14.38, P = 0.01] genotype and lower frequency of -174CC [OR (Recessive model) = 0.73, 95% CI = 0.54, 0.98, P = 0.03; OR (Codominant model) = 0.70, 95% CI = 0.51, 0.97, P = 0.03] genotype in Caucasians.

Our meta-analysis suggested that IL-6 promoter polymorphisms (-174G/C and -572G/C) were associated with intracranial aneurysms. However, due to the small subjects included in analysis and the selection bias in some studies, the results should be interpreted with caution.