Role of 4 platelet membrane glycoprotein polymorphisms on experimental arterial thrombus formation in men.
This study investigates whether the polymorphisms of 3 important platelet receptors affected experimental thrombus formation in men. Forty healthy male volunteers randomly recruited were genotyped for the variable number of tandem repeat (VNTR) of GPIbalpha, the -5T/C polymorphism in the Kozak sequence of GPIbalpha, the 807C/T polymorphism of GPIa, and the PI(A1)/PI(A2) polymorphism of GPIIb/IIIa. Platelet thrombus formation was induced ex vivo by exposing a collagen-coated coverslip in a parallel plate perfusion chamber to native blood for 4 minutes. The shear rates at the collagen surface were 650 and 2600 x s(-1). At 2600 x s(-1) platelet thrombus formation was significantly related only to the 807C/T polymorphism. In contrast, at 650 x s(-1) thrombus formation was significantly altered only by the Kozak sequence polymorphism. The VNTR and the PI(A1)/PI(A2) polymorphisms did not influence thrombus formation. Thus, platelet thrombus formation is significantly influenced by genetic variations of the GPIbalpha and GPIa receptors. The effect of these polymorphisms was dependent on the blood flow rate.
Cadroy
Y
Y
Laboratoire de Recherche sur l'Hémostase et la Thrombose, Pavillon Lefèbvre, and Centre d'Investigation Clinique, CHU Purpan, Toulouse Cedex, France. cadroy.y@chu-toulouse.fr
Sakariassen
K S
KS
Charlet
J P
JP
Thalamas
C
C
Boneu
B
B
Sie
P
P
D000328:Adult; D019943:Amino Acid Substitution; D015703:Antigens, CD / Q000235:genetics; D016824:Antigens, Human Platelet / Q000235:genetics* / Q000502:physiology; D001157:Arterial Occlusive Diseases / Q000097:blood / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018056:Hemorheology; D006801:Humans; D039421:Integrin alpha2; D008297:Male; D018598:Minisatellite Repeats; D010477:Perfusion; D010973:Platelet Adhesiveness / Q000235:genetics*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000235:genetics; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000235:genetics; D011110:Polymorphism, Genetic; D013927:Thrombosis / Q000097:blood / Q000235:genetics*
D015703:Antigens, CD; D016824:Antigens, Human Platelet; D039421:Integrin alpha2; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D019038:Platelet Glycoprotein GPIb-IX Complex