Endothelial nitric oxide synthase and fractalkine chemokine receptor polymorphisms on angiographically assessed coronary atherosclerosis.
BACKGROUND
The CX3CR1 is a fractalkine chemokine receptor expressed by leukocytes attracting them to the arterial wall inflammation. The endothelial nitric oxide synthase (eNOS) produces nitric oxide that acts on the vascular wall and circulating blood cells, lessening the inflammatory atherogenic damage. We determined if -786T > C and E298D eNOS and 745G>A CX3CR1 variants were associated with CAD risk and/or severity in Southern Brazilians of European descent.


METHODS
We investigated these polymorphisms in 358 patients who had undergone coronary angiography and 129 non-symptomatic controls by PCR followed by restriction analyses.


RESULTS
The 745 G > A CX3CR1 variant was not associated with CAD in this sample. Patients with significant CAD (coronary stenosis >or = 75%) presented higher frequencies of the eNOS -786C, but not of 298D allele than those observed among patients in whom significant CAD was ruled out by angiography (control group 1, p = 0.022) and non-symptomatic controls (control group 2, p < 0.001). The eNOS haplotypes derived from these 2 sites revealed that the frequency of haplotypes carrying the -786C allele (-786C/298D and -786C/298E) was increased and of the wild haplotype (-786T/298E) was decreased in patients with significant CAD (p = 0.003). After controlling for other classical risk factors carriers of haplotypes containing the -786C allele were at increased CAD risk (-786C/298D, OR = 2.95, p = 0.007; and -786C/298E, OR = 2.41, p = 0.030).


CONCLUSIONS
The -786T > C was the polymorphism associated with severe CAD in this study. Haplotype analyses can be extremely helpful in unraveling the influence of different markers within a gene.
Rios
Domingos L S
DL
Departamento de Genética, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Callegari-Jacques
Sídia M
SM
Hutz
Mara H
MH
D000073883:CX3C Chemokine Receptor 1; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000235:genetics* / Q000473:pathology*; D005260:Female; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D018121:Receptors, Cytokine / Q000235:genetics*; D015728:Receptors, HIV / Q000235:genetics*
D000073883:CX3C Chemokine Receptor 1; D018121:Receptors, Cytokine; D015728:Receptors, HIV; D052250:Nitric Oxide Synthase Type III