Vienna Stroke Registry. Impact of the platelet glycoprotein Ib alpha Kozak polymorphism on the risk of ischemic cerebrovascular events: a case-control study.
We performed a multicenter case-control study to evaluate the impact of the glycoprotein 1b alpha (-5)T/C Kozak polymorphism on the risk of ischemic cerebrovascular events. The genetic analysis in 1399 patients (745 men; median age, 70 years; interquartile ratio, 58-78) and 1066 control subjects (549 men; median age, 47 years; interquartile ratio, 39-59) was carried out with mutagenically separated polymerase chain reaction. Homozygous C/C genotype carriers had a 3.5-fold increased risk for ischemic cerebrovascular events (95% confidence interval, 1.5-7.9, P = 0.003) over T/T or T/C genotype carriers together. The effect was independent of well-established atherosclerotic risk factors. Our findings could be explained by the reported gene dose effect of the Kozak polymorphism on the density of the glycoprotein 1b alpha/IX/V receptors on platelets. According to our data, the (-5)C Kozak allele may represent a candidate genetic susceptibility factor for ischemic cerebrovascular events.
Clinical Institute of Medical and Chemical Laboratory Diagnostics, AKH Wien.
Kety
K
Hsieh
Marion
M
Funk
Martin
M
Schillinger
Georg
G
Endler
Michael
M
Janisiw
Manuela
M
Reisinger
Petra
P
Unger
Stefan
S
Greisenegger
Wilfried
W
Lang
Wolfgang
W
Lalouschek
Christine
C
Mannhalter
D000328:Adult; D000368:Aged; D000483:Alleles; D001317:Austria / Q000453:epidemiology; D002545:Brain Ischemia / Q000453:epidemiology* / Q000235:genetics; D016022:Case-Control Studies; D015897:Comorbidity; D005260:Female; D018628:Gene Dosage; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics*; D008875:Middle Aged; D019038:Platelet Glycoprotein GPIb-IX Complex; D012306:Risk; D012307:Risk Factors; D019851:Thrombophilia / Q000235:genetics
D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D019038:Platelet Glycoprotein GPIb-IX Complex; C094990:adhesion receptor