Platelet GPIbalpha, GPIV and vWF polymorphisms and fatal pre-hospital MI among middle-aged men.
BACKGROUND
The binding of platelet glycoprotein (GP) Ib-IX-V receptor complex to subendothelial collagen via von Willebrand factor is the initial step of the formation of platelet thrombi following atherosclerotic plaque rupture. Platelet GPIV binds to collagen and/or thrombospondin and further activates platelets. Genetic variation in these proteins could associate with platelet aggregability and the risk of myocardial infarction (MI).


RESULTS
We studied the associations of polymorphisms of GPIbalpha, GPIV and von Willebrand factor with the extent of coronary atherosclerosis, coronary narrowing, and fatal MI in an autopsy series of 300 middle-aged, Caucasian Finnish men who had suffered sudden out-of-hospital death. 31% of men with MI under the age of 50 carried the GPIbalpha HPA-2 ThrThr/Kozak TT haplotype as opposed to 62% of control men (OR 0.27, 95% CI 0.08-0.93, P = 0.03). In addition, 7% of men with MI under the age of 50 carried the GPIV AA genotype versus 29% of control men (OR 0.16, 95% CI 0.03-0.98, P < 0.05). These associations were not due to any effects of these gene variants on the coronary atherosclerotic changes. The G/A polymorphism of the von Willebrand factor gene failed to show any association with MI or coronary atherosclerosis in this series of men.


CONCLUSIONS
The combined ThrThr/TT haplotype of GPIbalpha as well as the AA genotype of GPIV seem to decrease the risk of fatal MI among men during early middle-age.
Pellikka
Minna
M
Medical School/B-building, University of Tampere, Tampere, 33014, Finland.
Narhi
Lassi
L
Perola
Markus
M
Penttila
Antti
A
Karhunen
Pekka J
PJ
Mikkelsson
Jussi
J
D000328:Adult; D000368:Aged; D018955:CD36 Antigens / Q000235:genetics*; D003324:Coronary Artery Disease / Q000097:blood / Q000235:genetics / Q000401:mortality; D023921:Coronary Stenosis / Q000097:blood / Q000235:genetics / Q000401:mortality; D016757:Death, Sudden, Cardiac / Q000453:epidemiology*; D005387:Finland / Q000453:epidemiology; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000235:genetics* / Q000401:mortality*; D016017:Odds Ratio; D010974:Platelet Aggregation / Q000235:genetics*; D019038:Platelet Glycoprotein GPIb-IX Complex; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D018570:Risk Assessment; D014841:von Willebrand Factor / Q000235:genetics*
D018955:CD36 Antigens; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D019038:Platelet Glycoprotein GPIb-IX Complex; C094990:adhesion receptor; D014841:von Willebrand Factor