Effects of polymorphisms in chemokine ligands and receptors on susceptibility to coronary artery disease.
BACKGROUND
Atherosclerosis, the underlying disorder of coronary artery disease (CAD), is an inflammatory process involving multiple molecular pathways. Chemokine-mediated mechanisms are potent regulators of atherosclerosis. Genetic variations that alter such signaling pathways could affect susceptibility to CAD. We investigated the effect of 5 common variations of chemokine and chemokine receptor genes (SDF1-3'A, CCR5-delta32, CCR2-64I, CX3CR1-V249I and CX3CR1-T280M) on predisposition to CAD.


METHODS
The hypothesis was tested by screening the prevalence of the above polymorphisms in 210 angiographically diagnosed CAD patients (152 with history of acute coronary syndromes, 58 with stable disease) in comparison to 165 selected controls with negative coronary angiography. Genotyping was performed by PCR/RFLP analysis.


RESULTS
There were no significant differences among cases and controls concerning allelic and genotypic frequencies of SDF1-3'A, CCR5-delta32, CCR2-64I and CX3CR1-V249I variations. A borderline higher allelic frequency of the M280 variant was observed in controls compared to CAD group (adjusted OR=0.65, 95% CI: 0.35-0.99, p=0.05). Subjects carrying at least one copy of the M280 allele were significantly more common in the control group, suggesting an atheroprotective effect of this variant (adjusted OR=0.58, 95% CI: 0.35-0.97, p=0.04).


CONCLUSIONS
The study confers additional data in the field of genetic predisposition to CAD: it confirms the atheroprotective effect of the M280 variant in a completely different population and supports the role of the fractalkine-CX3CR1 pathway in atherosclerosis.
Apostolakis
Stavros
S
Laboratory of Clinical Virology, Faculty of Medicine, University of Crete, Heraklion 711 10, Crete, Greece.
Baritaki
Stavroula
S
Kochiadakis
Georgios E
GE
Igoumenidis
Nikolaos E
NE
Panutsopulos
Dimitrios
D
Spandidos
Demetrios A
DA
D000368:Aged; D000483:Alleles; D050197:Atherosclerosis; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D003324:Coronary Artery Disease / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D007249:Inflammation; D008024:Ligands; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D019707:Receptors, Chemokine / Q000235:genetics
D018925:Chemokines; D008024:Ligands; D019707:Receptors, Chemokine