Genetic control of chemokines in severe human internal carotid artery stenosis.
OBJECTIVE
Atherosclerosis is an inflammatory disease. Chemokines and chemokine receptors are known to be involved in atherogenesis. Common single nucleotide polymorphisms (SNPs) affect transcription in response to inflammatory stimuli. The aim of this study was to evaluate the correlations between MCP-1, RANTES, SDF-1, CCR2, and CCR5 gene polymorphisms with increased risk of internal carotid artery (ICA) stenosis.


METHODS
Hundred and twelve patients, consecutively recruited for ICA occlusive disease, and 282 controls were genotyped for MCP-1-2518G, RANTES-403A, CCR5Delta32, CCR2 V64I, and SDF-1-801A polymorphisms.


RESULTS
The frequency of the SDF-1A allele was significantly different between cases and controls: 0.32 vs. 0.20, respectively (OR 1.81; 95% CI 1.25-2.60; p=0.007). The frequency of the RANTES-403G allele was significantly higher in patients with stenosis >70% (OR, 2.45; 95% CI 1.12-5.71; p=0.015). No significant differences were observed with the other polymorphisms.


CONCLUSIONS
The reported results seem to correlate the polymorphisms of the genes encoding for SDF-1, RANTES with pathogenesis and progression of ICA occlusive disease. Although suggestive, these results need confirmation in prospective cross-sectional studies.
Dipartimento MCO, Università degli Studi di Milano, Via A. Di Rudinì, 8, I-20142 Milano, Italy. giorgio.ghilardi@unimi.it
Giorgio
G
Ghilardi
Maria Luisa
ML
Biondi
Olivia
O
Turri
Francesca
F
Pateri
Gianvico Melzi
GM
d'Eril
Roberto
R
Scorza
D000368:Aged; D000483:Alleles; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism; D002343:Carotid Artery, Internal / Q000378:metabolism; D016893:Carotid Stenosis / Q000235:genetics* / Q000378:metabolism; D018925:Chemokines / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism; D012307:Risk Factors
D018925:Chemokines; D019707:Receptors, Chemokine