Genetic diversity of CX3CR1 gene and coronary artery disease: New insights through a meta-analysis

Abstract 

A significant portion of current medical research is devoted to the pursuit of genetic markers that can be used to identify disease or predict susceptibility to disease. In such a quest many investigators hypothesized that genetic variations that alter signalling pathways involved in atherosclerosis affect susceptibility to coronary artery disease (CAD). Fractalkine (FKN) is a small cytokine involved in monocyte chemotaxis and activation. Two single nucleotide polymorphisms, V249I and T280M, have been identified in the receptor coding sequence of FKN. The polymorphisms alter ligand–receptor affinity and are believed to influence an individual's susceptibility to atherosclerosis. Several investigators have tested the latter hypothesis with inconsistent results. In order to clarify the effect of the two polymorphisms on susceptibility to CAD we performed a meta-analysis, using pooled data retrieved from seven case–control studies. In total, 2000 CAD patients and 2841 subjects without evidence of cardiovascular disease were included in the meta-analysis. The 280M allele was associated with a reduced risk for CAD in the heterozygous state. Consequently, this effect was attributed to the only 280M-containing haplotype: I₂₄₉M₂₈₀. The latter haplotype was found to be significantly more frequent in the control population's gene pool. Although we do not believe that the retrieved odds ratios render the T280M polymorphism a candidate genetic marker for clinical applications, we do believe that the above genotype–phenotype interaction is indicative of the strong associations between FKN-induced pathways and CAD.

Keywords: CX3CR1, Polymorphism, Coronary artery disease