Involvement of polymorphisms in the chemokine system in the susceptibilityfor coronary artery disease (CAD). Coincidence of elevated Lp(a) and MCP-1-2518 G/G genotype in CAD patients

The central role of chemokines in the pathogenesis of atherosclerosis has b een made clear. Recently polymorphisms in the gene regulatory region of MCP -l and in the promoter region of RANTES have been found, which increase the expression of these chemokines. We investigated the role of these polymorp hisms together with the chemokine SDF-1 - 801A and the chemokine receptors CCR2-64I and CCR5 Delta 32 mutations in 318 patients with coronary artery d isease (CAD) referred to coronary bypass surgery, comparing them with 320 h ealthy controls. The prevalence of the MCP-1 - 2518 G/G homozygotes was sig nificantly higher among CAD patients than among controls (P < 0.005; OR = 2 .2 (95% CI 1.25-3.92). The Lp(a) levels of CAD patients with G/G genotype w ere significantly higher than those in patients with G/A or A/A genotypes. No CAD patients homozygous for the CCR5 Delta 32 and CCR2-64I mutations hav e been found. The genotype distributions of the two alleles deviated from t he Hardy Weinberg equilibrium in patients, indicating that the numbers of h omozygotes were significantly lower than expected. The MCP-1 - 2518G varian t in homozygous form appears as a genetic risk factor for severe CAD. This genotype is associated with elevated Lp(a) levels in patients. Individuals homozygous for CCR2-64I or CCR5 Delta 32 mutations are at reduced risk for severe CAD. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.