Genetic linkage of Kozak sequence polymorphism of the platelet glycoprotein Ibalpha with human platelet antigen-2 and variable number of tandem repeats polymorphism, and its relationship with coronary artery disease

SummaryPlatelet glycoprotein Iba (GPIba) gene polymorphisms have been reported to affect the risk of developing coronary heart disease. Here, within the GPIba gene, we determine the association between the variable number of tandem repeats (VNTR), the -5C/T Kozak sequence dimorphism, and the human platelet antigen (HPA)-2 polymorphisms with occurrence of myocardial infarction (MI). Patients (n=180) presenting survivors of MI were compared to 180 controls matched by age, gender, and race. Carriers of VNTR-CD genotype had a 2-fold higher risk for MI compared to controls. The prevalence of VNTR-BC was lower among patients than among controls (P=.007). These data are in agreement with recent reports of increased plug formation by human platelets containing VNTRCD but no other VNTR genotypes. Among patients, the number of vessels severely occluded was greater among carriers of the D-allele (P=.019) or VNTR-CD (P=.026) and lower among carriers of the C-allele (P=.003) or VNTR-CC (P=.0009) compared to non-carriers of these alleles. No influence was seen with the Kozak or HPA-2 polymorphisms. Determination of VNTR of the GPIba gene may prove useful for identifying high-risk individuals for MI.

Download Full-text

Human Platelet Antigen 3 (HPA-3): Localization of the Determinant of the Alloantibody Leka (HPA-3a) to the C-Terminus of Platelet Glycoprotein IIb Heavy Chain and Contribution of O-Linked Carbohydrates

Thrombosis and Haemostasis ◽

10.1055/s-0038-1651638 ◽

1993 ◽

Vol 69 (05) ◽

pp. 485-489 ◽

Cited By ~ 23

Author(s):

Isabelle Djaffar ◽

Didier Vilette ◽

Dominique Pidard ◽

Jean-Luc Wautier ◽

Jean-Philippe Rosa

Keyword(s):

Amino Acids ◽

Heavy Chain ◽

Human Platelet ◽

Platelet Glycoprotein ◽

Fibrinogen Receptor ◽

C Terminus ◽

Platelet Antigen ◽

Human Platelet Antigen ◽

Determinant Structure ◽

Polymerase Chain

SummaryThe human platelet antigen (HPA) 3 system is expressed on GPIIb, one subunit of GPIIb-IIIa, the platelet fibrinogen receptor. It was recently shown that HPA-3 was associated with an Ile843/Ser polymorphism. To investigate further HPA-3 determinant structure, we localized an HPA-3a determinant, recognized by the alloantiserum Leka, within the last 29 amino acids of GPIIbα. This region encompasses the polymorphic Ile843, which, as expected, is substituted into Ser in Leka-negative individuals, as shown by DNA sequence after polymerase chain reaction on platelet RNA. In addition, contribution of glycosylation to the determinant structure was demonstrated since the Leka antigenicity was strongly decreased after specifically removing nonterminal O-linked sugars, but not terminal sialic acids. We have thus refined the localization of an HPA-3a determinant within the last 29 amino acids, including Ile843, of GPIIb heavy chain, and shown that the Leka HPA-3a determinant is dependent, in part, upon the serine-linked carbohydrates adjacent to Ile/Ser843.

Download Full-text

Human platelet antigen allele frequencies and new mutations on platelet glycoprotein genes in the Chinese Han population

Transfusion Medicine ◽

10.1111/j.1365-3148.2011.01081.x ◽

2011 ◽

Vol 21 (5) ◽

pp. 330-337 ◽

Cited By ~ 8

Author(s):

X. Xu ◽

Y. Liu ◽

Y. Ying ◽

S. Tao ◽

X. Hong ◽

...

Keyword(s):

Human Platelet ◽

Allele Frequencies ◽

Chinese Han Population ◽

Platelet Glycoprotein ◽

Chinese Han ◽

Han Population ◽

Platelet Antigen ◽

Human Platelet Antigen ◽

New Mutations

Download Full-text

Association of a Variable Number of Tandem Repeats (VNTR) in Glycoprotein Ibα and HPA-2 Alloantigens

Thrombosis and Haemostasis ◽

10.1055/s-0038-1648954 ◽

1994 ◽

Vol 72 (05) ◽

pp. 757-761 ◽

Cited By ~ 31

Author(s):

S Simsek ◽

P M M Bleeker ◽

C E van der Schoot ◽

A E G Kr von dem Borne

Keyword(s):

Amino Acid ◽

Tandem Repeats ◽

Mononuclear Cells ◽

Human Platelet ◽

Strong Association ◽

Variable Number ◽

Platelet Glycoprotein ◽

Globular Domain ◽

Vntr Polymorphism ◽

Pcr Products

SummaryThe human platelet alloantigen HPA-2 (Koa/Kob) system is involved in two clinical syndromes, neonatal alloimmune thrombocytopenia and platelet transfusion refractoriness. Wb have previously described that the human platelet alloantigens HPA-2a(Kob) and HPA-2b(Koa), are caused by a Thrl45Met amino acid polymorphism in the N-terminal globular domain of the human platelet glycoprotein (GP) Ibα. In the present study the question was addressed as to whether a genetic association exists between this Thrl45Met polymorphism and the recently described variable number of tandem repeat (VNTR) polymorphism in GP Ibα. Such an association has already been suggested by serological analysis (Ishida et al., 1991). This VNTR polymorphism results from a 13-amino-acid sequence repeat in the macroglycopeptide region of GP Ibα. Therefore, we developed a PCR method to analyze the VNTR region of 106 normal individuals who were also analyzed for the HPA-2 polymorphism. In this method genomic DNA derived from mononuclear cells was purified, the polymorphic region was amplified by PCR and was electrophoresed on agarose gels. Differences in the size of the PCR products made VNTR typing possible. Genotyping for the HPA-2 system was done by allele-specific restriction site analysis of PCR products with the restriction enzyme Sfa NI. The DNA derived from 12 HPA-2 (a-b+) subjects, contained only the B variant (with 3 repeats) of the VNTR polymorphism. The D variant (with 1 repeat) was only found in HPA-2a positive individuals. The C variant (with 2 repeats) was found to be strongly associated with HPA-2a. However, two members of a family with a HPA-2 (a+b+) genotype were found to be homozygous for the C variant of the VNTR polymorphism. This shows that the C variant can also be associated with HPA-2b. The A variant (with 4 repeats) was not encountered in the population studied. The strong association of HPA-2 and VNTR polymorphism, lying 761 bp apart on the GP Ibα gene, indicates linkage disequilibrium.

Download Full-text

Polymorphism of Platelet Membrane Glycoprotein IIIa: Human Platelet Antigen 1b (HPA-1b/PlA2) Is an Inherited Risk Factor for Premature Myocardial Infarction in Coronary Artery Disease

Thrombosis and Haemostasis ◽

10.1055/s-0037-1615054 ◽

1998 ◽

Vol 79 (04) ◽

pp. 731-735 ◽

Cited By ~ 58

Author(s):

Rainer Zotz ◽

Bernhard Winkelmann ◽

Markus Nauck ◽

Günther Giers ◽

Beate Maruhn-Debowski ◽

...

Keyword(s):

Myocardial Infarction ◽

Coronary Artery Disease ◽

Risk Factor ◽

Coronary Artery ◽

Human Platelet ◽

Recent Onset ◽

Platelet Antigen ◽

Glycoprotein Iiia ◽

Human Platelet Antigen ◽

Artery Disease

SummaryConflicting results of an association between the human platelet antigen 1b (HPA-1b or PlA2) allele and the risk of myocardial infarction and coronary artery disease have been reported. To assess the reason for this discrepancy, we determined the HPA-1 genotype in 298 men who had undergone coronary angiography, including 124 individuals with myocardial infarction, 83 individuals with coronary artery disease but no history of myocardial infarction, and 91 control patients. Among patients with acute or recent onset myocardial infarction (<1 year), the prevalence of HPA-1b was higher than among patients with coronary artery disease but without myocardial infarction (33 percent vs. 14 percent, p = 0.016). In patients under 60 years of age this difference was even more pronounced (45 percent vs. 15 percent, p = 0.003). Unlike conventional risk factors HPA-1b does not represent a risk factor for coronary artery disease itself but appears to be associated with increased platelet thrombogenicity.

Download Full-text