title: Platelet functional implications of glycoprotein Ibalpha polymorphisms in African Americans.
abstract: The platelet glycoprotein Ibalpha is crucial in the binding of platelets to Von Willebrand Factor within areas of high stress. A single nucleotide polymorphism of GP Ibalpha gives rise to the Ko(a) (HPA-2b) and the -5C Kozak polymorphism. The presence of these polymorphisms has been associated with an increased risk for atherothrombotic disease. The Ko(a) polymorphism has been shown to have a higher prevalence in African Americans compared to American Caucasians. However, very little is known regarding any functional consequences of these platelet polymorphisms in African Americans. We assessed the prevalence of the Ko and -5C Kozak polymorphisms in a population of both African American and American Caucasian patients with and without CAD and determined whether there were platelet functional consequences in both groups. We studied 99 patients of which 22 were African American and 77 were American Caucasian. Aggregations were performed and shear induced platelet plug formation was tested using a platelet function analyzer. The HPA-2b allele was significantly higher in African Americans when compared to Caucasians (P = 0.001). Genotype frequencies of the -5C Kozak polymorphism were not significantly different between the two groups. We found no differences in platelet aggregation in African Americans who were either heterozygous or homozygous for the HPA-2b allele or the -5C Kozak allele when compared to American Caucasians of the same category. We found no significant differences in PFA-100 testing. We conclude from our study that these polymorphisms do not lead to altered platelet function in African Americans.
authors.affiliation: Department of Medicine, Johns Hopkins Medical Institute, Baltimore, Maryland, USA. mswillia@jhmi.edu
authors.forename: Marlene S
authors.initials: MS
authors.lastname: Williams
authors.forename: Ladina S
authors.initials: LS
authors.lastname: Ng'alla
authors.forename: Dhananjay
authors.initials: D
authors.lastname: Vaidya
mesh_terms: D001741:Black or African American; D000368:Aged; D000483:Alleles; D016824:Antigens, Human Platelet / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000235:genetics*; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D013927:Thrombosis / Q000235:genetics; D014481:United States; D044465:White People
chemical_list: C071221:2b alloantigen, human; D016824:Antigens, Human Platelet; D019038:Platelet Glycoprotein GPIb-IX Complex