Adverse associations between CX3CR1 polymorphisms and risk of cardiovascular or cerebrovascular disease.
OBJECTIVE
We investigated the role of monocyte-recruiting chemokines in cerebrovascular diseases among the subjects of the GENIC case-control study of brain infarction (BI).


RESULTS
Of the genotypes tested, only homozygosity for the rare CX3CR1 alleles was more frequent in cases than in controls: the I249 and M280 alleles were associated with an increased risk of BI (OR, 1.66 and OR, 2.62 with P<0.05, respectively). This effect was independent of other established risk factors and uncorrelated with disease severity. The study confirmed previous reports of a dominant protective association between CX3CR1-I249 allele and the risk of cardiovascular history. The risk of BI associated with homozygosity for the rare CX3CR1 alleles was enhanced in patients with no previous cardiovascular events. Ex vivo studies showed that the number of monocytes adhering to immobilized CX3CL1, the CX3CR1 ligand, increased proportionally to the number of CX3CR1 mutated alleles carried by the individual.


CONCLUSIONS
The rare CX3CR1 alleles were associated with an increased risk of BI and with reduced frequency of cardiovascular history. We propose that the extra adhesion of monocytes observed in individuals carrying rare alleles of CX3CR1 may favor mechanisms leading to stroke.
Lavergne
Elise
E
Laboratoire d'Immunologie Cellulaire, INSERM U543, Hôpital Pitié-Salpêtrière, Paris, France.
Labreuche
Julien
J
Daoudi
Mehdi
M
Debré
Patrice
P
Cambien
François
F
Deterre
Philippe
P
Amarenco
Pierre
P
Combadière
Christophe
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001161:Arteriosclerosis / Q000453:epidemiology* / Q000235:genetics* / Q000276:immunology; D000073883:CX3C Chemokine Receptor 1; D016022:Case-Control Studies; D002544:Cerebral Infarction / Q000453:epidemiology / Q000235:genetics / Q000276:immunology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005838:Genotype; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology; D009203:Myocardial Infarction / Q000453:epidemiology / Q000235:genetics / Q000276:immunology; D011110:Polymorphism, Genetic; D019707:Receptors, Chemokine / Q000235:genetics*; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology / Q000235:genetics / Q000276:immunology
D000073883:CX3C Chemokine Receptor 1; C095235:CX3CR1 protein, human; D008565:Membrane Proteins; D019707:Receptors, Chemokine