Influence of interleukin-6 gene −174G>C polymorphism on development of atherosclerosis: A meta-analysis of 50 studies involving 33,514 subjects

• Published in: Gene Vol. 529; no. 1; pp. 94 - 103
• Main Authors: Yin, Yan-Wei, Li, Jing-Cheng, Zhang, Meng, Wang, Jing-Zhou, Li, Bing-Hu, Liu, Yun, Liao, Shao-Qiong, Zhang, Ming-Jie, Gao, Chang-Yue, Zhang, Li-Li
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.10.2013
• Subjects: Alleles; Atherosclerosis; Atherosclerosis - genetics; clinical trials; confidence interval; Databases, Factual; epidemiological studies; Ethnic Groups - genetics; Genetic Predisposition to Disease; Genome-Wide Association Study; Genotype; Humans; Interleukin-6; Interleukin-6 - genetics; Meta-analysis; nationalities and ethnic groups; Odds Ratio; Polymorphism; Polymorphism, Genetic; risk; Risk Factors; Sensitivity and Specificity; RAO; AAA; PAOD; OR; RAS; CI; CAD; PRISMA; MeSH; IS; TIA; IL-6; Interleukin-6; Meta-analysis; AS; PAD; NOS; HWE; Atherosclerosis; MI; CVDs; CHD; Polymorphism; coronary artery disease; Preferred Reporting Items for Systematic Reviews and Meta-analyses; myocardial infarction; odds ratio; abdominal aortic aneurysm; Newcastle-Ottawa Scale; Hardy–Weinberg equilibrium; ischemic stroke; Medical Subject Heading; retinal artery occlusion; peripheral artery occlusive disease; cardiovascular diseases; peripheral Arterial Disease; transient ischemic attack, CAS carotid artery stenosis; renal artery stenosis; confidence interval; coronary heart disease
• ISSN: 0378-1119; 1879-0038; 1879-0038
• DOI: 10.1016/j.gene.2013.07.074

Increasing epidemiological studies have focused on the associations between interleukin-6 (IL-6) gene −174G>C polymorphism and atherosclerotic diseases, but the results are still controversial. This meta-analysis was designed to identify whether this association exists. PubMed, Embase, Web of Science, Cochrane database, Clinicaltrials.gov and Current Controlled Trials, Chinese Clinical Trial Registry, CBMdisc, CNKI and Google Scholar were searched to get the genetic association studies. The crude odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were used to estimate the association between the IL-6 gene −174G>C polymorphism and atherosclerosis ( AS ) risk. The subgroup analyses were made on the following: ethnicity, atherosclerotic diseases and source of controls. Finally, 50 studies (15,029 cases and 18,485 controls) were included in this meta-analysis. Overall, no significant association was found between the IL-6 gene −174G>C polymorphism and AS risk (for C allele vs. G allele: OR=1.02, 95% CI=0.94–1.11, p=0.64; for C/C vs. G/G: OR=1.01, 95% CI=0.85–1.21, p=0.88; for C/C vs. C/G+G/G: OR=0.97, 95% CI=0.84–1.12, p=0.68; for C/C+C/G vs. G/G: OR=1.07, 95% CI=0.97–1.17, p=0.18). In the subgroup analyses, significant associations were found between the IL-6 gene −174G>C polymorphism and AS in non-Caucasian group (for CC+CG vs. GG: OR=1.22, 95% CI=1.06–1.41, p=0.005), other atherosclerotic diseases group (for C allele vs. G allele: OR =0.75, 95% CI=0.61–0.93, p=0.008; for C/C vs. G/G: OR=0.56, 95% CI=0.38–0.81, p=0.002; for C/C vs. C/G+G/G: OR=0.60, 95% CI=0.45–0.79, p=0.0004) and population-based group (for C allele vs. G allele: OR=1.09, 95% CI=1.00–1.18, p=0.04; for CC+CG vs. GG: OR=1.15, 95% CI=1.04–1.27, p=0.005). In summary, the present meta-analysis suggests that the IL-6 gene −174GC polymorphism is associated with the susceptibility to AS. However, due to the high heterogeneity in the meta-analysis, the results should be interpreted with caution. •We performed a meta-analysis to derive a more precise estimation of the relationship.•Our study has the potential to detect small effects in genetic association studies.•Our study suggests that IL-6 gene −174G>C polymorphism is associated with AS risk.