Association of interleukin-6 gene polymorphism with coronary artery disease: an updated systematic review and cumulative meta-analysis

Interleukin-6 (IL-6) is an important mediator of atherosclerotic disease and is also associated with coronary artery disease (CAD). The growing evidences suggest that polymorphisms in the IL-6 promoter region influence the progression of CAD. This study was performed to update the systematic results of association of IL-6 gene polymorphisms with CAD. PubMed, Embase, and China Biology Medicine were searched systematically for English and Chinese articles published up to October 31, 2014. Data were extracted using standardized forms. Odds ratios (ORs) with 95 % confidence intervals (CIs) were used to assess the strength of associations. Subgroup analyses were made on ethnicity. A total of 42 studies including 15,145 cases and 21,496 controls were combined in this meta-analysis. IL-6 gene -174G/C polymorphism was associated with an increased risk of CAD (for C allele versus G allele: OR = 1.11, 95 % CI 1.02-1.20; for C/C versus G/G: OR = 1.21, 95 % CI 1.03-1.42; for C/C + C/G versus G/G: OR = 1.14, 95 % CI 1.03-1.27). In the subgroup analyses based on ethnicity, a significant association was found between -174 G/C polymorphism and CAD in Caucasians (for C allele versus G allele: OR = 1.12, 95 % CI 1.03-1.22; for C/C versus G/G: OR = 1.21, 95 % CI 1.02-1.42; for C/C + C/G versus G/G: OR = 1.16, 95 % CI 1.05-1.29). In order to reduce heterogeneity, we removed the outlier studies by a Galbraith plot analysis. As a result, the pooled ORs demonstrated no association of -174G/C polymorphism and CAD (C allele versus G allele: OR = 1.02, 95 % CI 0.97-1.06, p = 0.48; C/C versus G/G: OR = 0.1.03, 95 % CI 0.94-1.13, p = 0.48; C/G + C/C versus G/G: OR = 1.03, 95 % CI 0.96-1.09, p = 0.41; C/C versus C/G + G/G: OR = 1.02, 95 % CI 0.94-1.10, p = 0.70, respectively). The polymorphism of -572 G/C was not associated with CAD significantly (for C allele versus G allele: OR = 0.86, 95 % CI 0.74-1.01; C/C versus G/G: OR = 0.99, 95 % CI 0.43-2.27; C/G + C/C versus G/G: OR = 0.96, 95 % CI 0.80-1.15, respectively). In addition, subgroup analyses showed an association between -572 G/C polymorphism and CAD risk among Chinese (C allele versus G allele: OR = 0.64, 95 % CI 0.48-0.85; C/C versus G/G: OR = 0.38, 95 % CI 0.18-0.81; C/G + C/C versus G/G: OR = 0.47, 95 % CI 0.22-1.00; C/C versus C/G + G/G: OR = 0.58, 95 % CI 0.42-0.81). The C allele of -174G/C polymorphism may associate with increased sensibility to CAD among Caucasians in overall analysis. Nevertheless, the effect is interfered by heterogeneity across the included studies. The C allele of -572G/C polymorphism may decrease the risk of CAD in Chinese.