Hsieh Kety, Funk Marion, Schillinger Martin, Endler Georg, Janisiw Michael, Reisinger Manuela, Unger Petra, Greisenegger Stefan, Lang Wilfried, Lalouschek Wolfgang, Mannhalter Christine
Clinical Institute of Medical and Chemical Laboratory Diagnostics, AKH Wien.
Blood Coagul Fibrinolysis. 2004 Sep;15(6):469-73. doi: 10.1097/00001721-200408000-00005.
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.
