Type

Journal Article

Authors

Denis C Shields
Desmond J Fitzgerald
John K O'Brien
Anthony Fitzgerald
Michelle Dooley
Fiona O'Connor
Ronan Curtin
Aisling M O'Halloran

Subjects

Biochemistry

Topics
blood platelets humans metabolism platelet aggregation platelet glycoprotein gpiib iiia complex analysis of variance statistics nonparametric hypertension integrin beta3 reverse transcriptase polymerase chain reaction glycoprotein receptor gpib ix platelet membrane glycoproteins platelet glycoprotein gpib ix complex genetics platelet count coronary disease heterozygote polymorphism genetic blood promoter regions genetic haplotypes rna

The impact of genetic variation in the region of the GPIIIa gene, on Pl expression bias and GPIIb/IIIa receptor density in platelets. (2006)

Abstract Some studies have suggested that genetic variability in the glycoprotein (GP) IIIa gene modulates expression of platelet GPIIb/IIIa (alpha(2b)beta(3)). We sought to determine as to whether combinations of genetic variants within the GPIIIa gene (haplotypes) influenced the expression of GPIIIa RNA and protein levels in human platelets. Three promoter polymorphisms, Pl(A1/A2) genotype and platelet receptor densities were determined in 207 acute coronary syndrome (ACS) patients. Allele-specific quantitative reverse transcription-polymerase chain reaction of platelet RNA from Pl(A1/A2) heterozygotes identified a greater expression of Pl(A2) bearing transcripts among heterozygotes. Among the patients studied, the ratio of Pl(A1)/Pl(A2) RNA expression was significantly influenced by promoter haplotype (P < 0.01). However, this effect reflected carriership of rare not common haplotypes (P = 0.2). There was a threefold variation between subjects in the number of GPIIb/IIIa receptors expressed per platelet, although no association between receptor density and the Pl(A2) (P = 0.93) or promoter polymorphisms was demonstrated (-468A, P = 0.52; -425C, P = 0.59; -400A, P = 0.52). Among common haplotypes, Pl(A1)/Pl(A2) RNA expression was negatively correlated with adjusted GPIIb/IIIa receptor density (P = 0.04). The overall trend towards higher expression of Pl(A2) bearing message in Pl(A1/A2) heterozygotes, and the existence of rare haplotypes with more pronounced changes indicate the existence of cis-acting genetic factors that remain to be identified.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

Denis C Shields, Desmond J Fitzgerald, John K O'Brien, Anthony Fitzgerald, Michelle Dooley, Fiona O'Connor, Ronan Curtin, Aisling M O'Halloran

Experts in our system

1
Denis C. Shields
University College Dublin
Total Publications: 123
 
2
D J Fitzgerald
Royal College of Surgeons in Ireland
Total Publications: 101
 
3
Anthony P Fitzgerald
University College Cork
Total Publications: 78
 
4
Aisling O'Halloran
Trinity College Dublin
Total Publications: 34