A monocyte chemoattractant protein-1 gene polymorphism is associated with occult ischemia in a high-risk asymptomatic population

Monocyte chemoattractant protein-1 (MCP-1) recruits monocytes into atherosclerotic plaques. A single nucleotide polymorphism in the MCP-1 gene promoter (-2578A > G) results in greater production of MCP-1 protein. We examined the association of this polymorphism with occult coronary artery disease (CAD) and its interaction with CAD risk factor burden, as assessed by the Framingham risk score (FRS) for hard events. We genotyped 679 apparently healthy 24-59-year-old siblings (SIBS) of people with premature CAD, tested for occult ischemia with exercise treadmill tests and thallium-201 single photon emission computed tomography, and assessed CAD risk factors to calculate the FRS. Occult ischemia occurred in 18% of SIBS and overall was somewhat more prevalent in those with the G allele (20.6%) compared to those without (15.6%), p = 0.095. In SIBS at higher risk (highest quartile of FRS, ≥6.8%), occult ischemia occurred significantly more frequently in those with the G allele (44.4% versus 26.1%, p = 0.017), while there was no significant difference in SIBS with lower FRS. After adjusting for individual risk factors included in the FRS, multivariate logistic regression modeling demonstrated that the G allele independently predicted occult ischemia in the entire study population (p = 0.014, OR = 1.86, 95% CI = 1.14-3.04). This study demonstrates for the first time that the MCP-1 gene -2578A > G polymorphism is associated with an excess risk of coronary atherosclerosis in an asymptomatic population and demonstrates an apparent interaction with CAD risk factor burden.