Involvement of polymorphisms in the chemokine system in the susceptibility for 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 been made clear. Recently polymorphisms in the gene regulatory region of MCP-1 and in the promoter region of RANTES have been found, which increase the expression of these chemokines. We investigated the role of these polymorphisms together with the chemokine SDF-1-801A and the chemokine receptors CCR2-64I and CCR5Delta32 mutations in 318 patients with coronary artery disease (CAD) referred to coronary bypass surgery, comparing them with 320 healthy controls. The prevalence of the MCP-1 -2518 G/G homozygotes was significantly 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 were significantly higher than those in patients with G/A or A/A genotypes. No CAD patients homozygous for the CCR5Delta32 and CCR2-64I mutations have been found. The genotype distributions of the two alleles deviated from the Hardy Weinberg equilibrium in patients, indicating that the numbers of homozygotes were significantly lower than expected. The MCP-1 -2518G variant 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 CCR5Delta32 mutations are at reduced risk for severe CAD.
Szalai
C
C
Section of Molecular Immunology, Hungarian Academy of Sciences, Budapest, Hungary. szalai@heim.sote.hu
Duba
J
J
Prohászka
Z
Z
Kalina A
Szabó
T
T
Nagy
B
B
Horváth
L
L
Császár
A
A
D000328:Adult; D000368:Aged; D000483:Alleles; D018932:Chemokine CCL2 / Q000235:genetics; D018946:Chemokine CCL5 / Q000235:genetics; D054377:Chemokine CXCL12; D018925:Chemokines / Q000235:genetics*; D019743:Chemokines, CXC / Q000235:genetics; D003327:Coronary Disease / Q000097:blood / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006720:Homozygote; D006801:Humans; D017270:Lipoprotein(a) / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D054390:Receptors, CCR2; D019713:Receptors, CCR5 / Q000235:genetics; D019707:Receptors, Chemokine / Q000235:genetics; D012307:Risk Factors
C515334:CCR2 protein, human; C515255:CXCL12 protein, human; D018932:Chemokine CCL2; D018946:Chemokine CCL5; D054377:Chemokine CXCL12; D018925:Chemokines; D019743:Chemokines, CXC; D017270:Lipoprotein(a); D054390:Receptors, CCR2; D019713:Receptors, CCR5; D019707:Receptors, Chemokine