Abstract
Background: Previous studies have explored associations between interleukin-18 (IL-18) promoter polymorphisms and coronary artery disease (CAD). However, the results were controversial. We conducted a meta-analysis to clarify the association between the two polymorphisms and CAD risk. Methods: We searched English and Chinese databases and calculated the odds ratio (OR) and 95% confidence interval (CI) to estimate whether there are genetic associations between IL-18 promoter polymorphisms and the risk of CAD. All relevant studies were screened and meta-analyzed using STATA 15.0. Results: A total of 15 studies, including 12 studies for -137 G/C and 9 studies for -607 C/A, were identified for the meta-analysis. For -137 G/C, the results showed a significantly reduced risk of CAD in the dominant model (OR = 0.85) and heterozygous model (OR = 0.88) in the overall analysis. However, in subgroup analysis, decreased CAD risks were only observed in Asian populations for heterozygous genetic models. For -607 C/A, the overall OR revealed a reduced risk of CAD in all five genetic models (allelic, OR = 0.78; recessive, OR = 0.75; dominant, OR = 0.68; homozygous, OR = 0.61; heterozygous, OR = 0.72). In subgroup analysis, reduced CAD risk was also found in five genetic models of the Asian population. We also found that the IL-18 polymorphisms were correlated with myocardial infarction (MI) and multivessel (MV) disease. Conclusion: Our results suggested that the -137 polymorphism and -607 polymorphism in the IL-18 promoter were negatively associated with CAD, especially in the Asian population. In addition, some genetic models were correlated with the severity of CAD.
Highlights
Received: 14 August 2019Revised: 17 October 2019Accepted: 25 October 2019Accepted Manuscript online: Version of Record published: Coronary artery disease (CAD) is an important cause of cardiovascular mortality worldwide [1,2]
Three hundred and three articles were retrieved from the initial database search, 133 studies were screened for duplicates, case reports, in vitro or in vivo studies, meta-analysis, reviews, and the remaining articles (n=17) for secondary screening
In subgroup analysis by ethnicity, reduced coronary artery disease (CAD) risk was found in five genetic models of the Asian population (A vs. C, odds ratio (OR) = 0.62, 95% confidence interval (CI) = 0.55–0.70, P=0.000, I 2 = 0%; AA vs. CA+CC, OR = 0.63, 95% CI = 0.52–0.77, P=0.000, I 2 = 8.4%; AA+CA vs. CC, OR = 0.46, 95% CI = 0.38–0.55, P=0.000, I 2 = 0%; AA vs. CC, OR = 0.38, 95% CI = 0.30–0.48, P=0.000, I 2 = 0%, CA vs. CC, OR = 0.49, 95% CI = 0.40–0.61, P=0.000, I 2 = 0%)
Summary
Received: 14 August 2019Revised: 17 October 2019Accepted: 25 October 2019Accepted Manuscript online: Version of Record published: Coronary artery disease (CAD) is an important cause of cardiovascular mortality worldwide [1,2]. Several new cytokines have been identified to be associated with the development of CAD, such as interleukin-18 (IL-18) [4]. Promoter polymorphisms and coronary artery disease (CAD). We conducted a meta-analysis to clarify the association between the two polymorphisms and CAD risk. Methods: We searched English and Chinese databases and calculated the odds ratio (OR) and 95% confidence interval (CI) to estimate whether there are genetic associations between IL-18 promoter polymorphisms and the risk of CAD. Results: A total of 15 studies, including 12 studies for -137 G/C and 9 studies for -607 C/A, were identified for the meta-analysis. For -137 G/C, the results showed a significantly reduced risk of CAD in the dominant model (OR = 0.85) and heterozygous model (OR = 0.88) in the overall analysis
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