Cytokine polymorphisms associated with carotid intima-media thickness in stroke patients.
OBJECTIVE
Carotid intima-media thickness (IMT) reflects generalized atherosclerosis and is predictive of future vascular events. Evidence exists that carotid IMT is heritable, and genetic studies can provide clues in the pathogenesis of atherosclerosis.


METHODS
We recruited 470 white ischemic stroke patients, measured common carotid artery (CCA) IMT, and analyzed 54 polymorphisms with suspected roles in atherosclerosis.


RESULTS
Among the polymorphisms tested, the angiotensin-converting enzyme insertion/deletion, osteopontin (OPN) T-443C, monocyte chemoattractant protein-1 (MCP-1) G-927C, and MCP-1 A-2578G polymorphisms were associated with CCA-IMT in age-gender-adjusted analysis. In multivariate analysis, the association between the OPN and MCP-1 polymorphisms remained significant. The OPN-443C allele was associated with increased IMT in the dominant model (0.053 mm for the TC and CC genotypes; P=0.001). The MCP-1-927C allele was associated with increased IMT in the additive model (0.040 mm for each C allele; P=0.001), and the MCP-1-2578 G allele was associated with decreased IMT in the recessive model (0.088 mm for the GG genotype; P=0.002).


CONCLUSIONS
The OPN and MCP-1 genes, coding for 2 cytokines with known roles in atherosclerosis, may contribute to increased carotid IMT and warrant further study.
Brenner
David
D
Department of Neurology and Stroke Centre, Bichat University Hospital, Denis Diderot University and Medical School, Paris, France.
Labreuche
Julien
J
Touboul
Pierre-Jean
PJ
Schmidt-Petersen
Klaus
K
Poirier
Odette
O
Perret
Claire
C
Schönfelder
Jacqueline
J
Combadière
Christophe
C
Lathrop
Mark
M
Cambien
François
F
Brand-Herrmann
Stefan-Martin
SM
Amarenco
Pierre
P
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001798:Blood Proteins / Q000235:genetics; D002545:Brain Ischemia / Q000235:genetics; D002340:Carotid Artery Diseases / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D017536:Carotid Artery, Common / Q000000981:diagnostic imaging / Q000648:ultrastructure*; D018932:Chemokine CCL2 / Q000235:genetics* / Q000502:physiology; D004798:Enzymes / Q000235:genetics; D005260:Female; D005602:France / Q000453:epidemiology; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D053495:Osteopontin; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D012307:Risk Factors; D012795:Sialoglycoproteins / Q000235:genetics* / Q000502:physiology; D017539:Tunica Intima / Q000000981:diagnostic imaging / Q000648:ultrastructure*; D017540:Tunica Media / Q000000981:diagnostic imaging / Q000648:ultrastructure*; D014463:Ultrasonography; D044465:White People / Q000235:genetics
D001798:Blood Proteins; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D004798:Enzymes; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; D053495:Osteopontin; D007703:Peptidyl-Dipeptidase A