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Increased platelet aggregability associated with platelet GPIIIa PlA2 polymorphism: the Framingham Offspring Study
D Feng1, K Lindpaintner, M G Larson
1Institute for Prevention of Cardiovascular Disease, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Arteriosclerosis, Thrombosis, and Vascular Biology
|April 9, 1999
Summary
The PlA2 genetic variant of platelet glycoprotein IIIa is linked to higher platelet reactivity, potentially explaining its association with increased cardiovascular disease risk.
Area of Science:
- Cardiovascular Genetics
- Hematology
- Molecular Biology
Background:
- Platelet glycoprotein IIb/IIIa (GP IIb/IIIa) is crucial for platelet aggregation.
- The PlA2 polymorphism in GPIIIa is suspected to increase cardiovascular disease risk.
- The relationship between PlA2 polymorphism and platelet reactivity remains unclear.
Purpose of the Study:
- To investigate the association between GP IIIa genotype (PlA1/PlA2 polymorphism) and platelet reactivity.
- To determine if the PlA2 variant influences platelet aggregability in response to agonists.
Main Methods:
- Genotyping for GP IIIa PlA1/PlA2 polymorphism in 1422 subjects using PCR-RFLP.
- Assessing platelet aggregability via the Born method, determining threshold concentrations for epinephrine and ADP.
- Statistical analysis to evaluate the impact of PlA2 alleles on platelet reactivity.
Main Results:
- Allele frequencies: PlA1 (0.84) and PlA2 (0.16).
- Individuals with PlA2 alleles showed significantly increased platelet aggregability, indicated by lower epinephrine threshold concentrations (P=0.009).
- This association remained significant after adjusting for covariates (P=0.007). ADP-induced aggregation showed a trend but was not statistically significant after adjustment (P=0.19).
Conclusions:
- Molecular variants of the GP IIIa gene influence in vitro platelet reactivity.
- The findings provide a mechanistic explanation for the observed link between the PlA2 allotype and heightened cardiovascular disease risk.