RANTES gene G-403A polymorphism and coronary artery disease: a meta analysis of observational studies

Abstract

Objective: The G-403A polymorphism in RANTES gene may be involved in the development of coronary artery disease (CAD) through increasing RANTES-mediated leukocyte trafficking and activation. However, studies investigating the relationship between G-403A polymorphism and CAD yielded contradictory and inconclusive results. In order to shed some light on these inconsistent findings, a meta analysis was performed to clarify the role of G-403A polymorphism of RANTES gene in the susceptibility of CAD.

Methods: A systemic literature search of PubMed and EMBASE was conducted from their inception to March 23, 2012, to retrieve related studies. In addition, Conference Proceedings Citation Index-Science was searched, authors of relevant studies were contacted, and reference lists of the included studies and their related citations in PubMed were reviewed for additional pertinent studies.

Results: A total of 8 eligible studies were identified, with a total of 4252 CAD cases and 2150 controls. There was no evidence of significant association between G-403A polymorphism and CAD risk in any genetic model or pairwise comparisons (additive model: OR = 1.046, 95% CI = 0.883-1.239, I(2) = 65.9%; recessive model: OR = 1.140, 95% CI = 0.774-1.678, I(2) = 53.1%; dominant model: OR = 1.000, 95% CI = 0.820-1.21), I(2) = 62.6%; AA vs GG: OR = 1.141, 95% CI = 0.734-1.773, I(2) = 61.2%; GA vs GG: OR = 0.993, 95% CI = 0.800-1.232, I(2) = 64.6%). Subgroup analysis and meta regression indicated that ethnicity and genotyping method accounted for the significant heterogeneity among studies. In the stratified analysis by ethnic group, G-403A polymorphism was found to be associated with increased CAD risk in Caucasian population whereas its protective role was observed in Asian population in some but not all comparisons.

Conclusion: Data from the current meta-analysis do not support the existence of a relationship between G-403A polymorphism and the development of CAD, and large sample size study employing unified genotyping method is needed to further evaluate the influence of G-403A polymorphism on susceptibility of CAD.

Figure 1. Flow diagram of literature identification and filtration in the systematic review.

Figure 2. Results of association between the G-403A polymorphism and coronary artery disease.

The overall odds ratio (OR) was estimated with DerSimonian-Laird random effects model. The ORs of individual studies are shown as squares, with the size proportional to the weight of each study in the overall estimate; 95% confidence intervals (CIs) are shown as horizontal lines. The pooled OR and its 95% CI are shown as a dashed vertical line and a diamond, respectively. A, Additive model. B, Recessive model. C, Dominant model. D, AA versus GG. E, GA versus GG.

Figure 3. Begg’s funnel plot of publication bias with pseudo 95% confidence limits.

The horizontal line in the funnel plot indicates the random effects summary estimate, while the sloping lines indicate the expected 95% confidence intervals for a given standard error, assuming no heterogeneity between studies. Each study is represented by a circle, the area of which represents the study’s precision. A, Additive model (Egger’s test P = 0.643). B, Recessive model (Egger’s test P = 0.020 ). C, Dominant model (Egger’s test P = 0.519). D, AA versus GG (Egger’s test P = 0.014). E, GA versus GG (Egger’s test P = 0.429).