Genetic variants of the monocyte chemoattractant protein-1 gene and its receptor CCR2 and risk of coronary artery disease: a meta-analysis

Objective: Monocyte chemoattractant protein-1 (MCP-1) and its receptor chemokine (C-C motif) receptor 2 (CCR2) are implicated in promoting atherosclerosis. Many studies have searched the association between variants of the MCP-1 gene or CCR2 gene and risk of coronary artery disease (CAD), but the results are inconsistent.

Methods: We conducted a meta-analysis of 20 publications including 24 studies on 2 genetic variants [A-2518G in the MCP-1 and V64I in the CCR2] published before January 2011, including a total of 9844 patients with CAD and 11,821 controls. Publication bias and heterogeneity among studies were explored.

Results: In a combined analysis, the pooled OR for CAD of the -2518G allele was 1.42 (95%CI: 1.06-1.92) compared to wild-type A allele under a recessive model in Caucasian group, but there is an indication of publication bias and heterogeneity among the 9 studies. When the analyses were restricted to 2 large studies (n≥500 cases), the pooled OR was 1.08 (95%CI: 0.85-1.37). Our analyses detected a possibility of publication bias with an overestimate of the true association by smaller studies. A meta-analysis of studies on the CCR2 V64I variant showed no significant association with CAD, the pooled OR of 64I was 1.27 (95%CI: 0.81-1.99) in recessive model and 1.06 (95%CI: 0.95-1.19) in dominant model, respectively.

Conclusions: The results indicate that MCP-1-2518G allele had probably increased risk of CAD in Caucasian but this is likely to be due to publication bias and insufficient sample size. The CCR2 V64I has not been found any association with CAD.