Prothrombotic genetic variants and atherosclerosis in patients with cerebral ischemia of arterial origin.
OBJECTIVE
Prothrombotic genetic variants associated with arterial disease probably affect arterial thrombus formation but may also promote atherosclerosis. We hypothesized that specific prothrombotic variants lead to advanced atherosclerosis in patients with cerebral ischemia of arterial origin.


RESULTS
We included 689 patients with nondisabling cerebral ischemia of arterial origin. Twenty-two variants in 14 genes were genotyped. None of the variants was associated with carotid intima-media thickness or younger age at the occurrence of cerebral ischemia. Factor V Leiden (mean prevalence difference 25%; 95% CI 11-40) and the glycoprotein 1b-alpha Thr145Met variant (mean prevalence difference 12%; 95% CI 2.3-22) were associated with symptomatic carotid stenosis. After accounting for multiple testing by determination of the false discovery rate, only the association between factor V Leiden and symptomatic carotid stenosis remained present.


CONCLUSIONS
Prothrombotic genetic variants showed no consistent association with three markers of advanced atherosclerosis in patients with cerebral ischemia of arterial origin. This study does not support the hypothesis that prothrombotic genetic variants have a direct role in the pathogenesis of atherosclerosis.
Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands.
D M O
DM
Pruissen
L J
LJ
Kappelle
F R
FR
Rosendaal
A
A
Algra
D000368:Aged; D050197:Atherosclerosis / Q000097:blood / Q000235:genetics* / Q000473:pathology; D002545:Brain Ischemia / Q000097:blood / Q000235:genetics*; D016893:Carotid Stenosis / Q000097:blood / Q000235:genetics* / Q000473:pathology; D015331:Cohort Studies; D005165:Factor V / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006487:Hemostasis / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000235:genetics; D018570:Risk Assessment; D012307:Risk Factors; D013927:Thrombosis / Q000097:blood / Q000150:complications / Q000235:genetics*
D019038:Platelet Glycoprotein GPIb-IX Complex; C095381:factor V Leiden; D005165:Factor V