Use this URL to cite or link to this record in EThOS:
Title: Platelet reactivity, polymorphisms and premature myocardial infarction
Author: Singh, Ravi Kumar
ISNI:       0000 0001 3415 8154
Awarding Body: University of Leicester
Current Institution: University of Leicester
Date of Award: 2005
Availability of Full Text:
Access from EThOS:
Access from Institution:
I have carried out a detailed assessment of platelet function and reactivity in 205 subjects that suffered a premature MI (at a mean age 42.3 +/- 5.7) and 200 age and sex matched controls, to two endogenous platelet agonists adenosine diphosphate (ADP) and thrombin receptor activating peptide (TRAP). I have further analysed the effect on platelet function of polymorphisms in two platelet receptors (GPIIbIIIa C196T and GPIaIIa G873A), which have been proposed as genetic risk factors for MI. Platelet reactivity to several concentrations of ADP and TRAP, measured as degree of fibrinogen binding by flow cytometry, showed marked inter-individual variation (4-5 fold) in both cases and controls. There was a strong correlation between the ADP and TRAP responses and experimental analysis suggested that this was because the TRAP response is substantially mediated via the ADP receptor.;Expression of the GPIaIIa receptor on the platelet surface showed up to 10-fold variation between subjects. The G837A polymorphism in the GP1a gene had a marked effect on GPIaIIa expression (accounting for about one-fifth of the variation) but did not influence the risk of MI (odd ratio 1.12 (95%CI 0.86-1.46)). Expression of the GPIIbIIIa receptor in both the resting state and after agonist stimulation was not affected by C196T polymorphism in the GPIIIa gene and did not influence risk of MI (odds ratio=0.94 (0.61-1.45)).;Of the emerging risk factors, fibrinogen (p<0.001) and Lp(a) (p = 0.016) were higher in the cases. There were significant effect of the G455A polymorphism in the fibrinogen beta chain gene and the C93T polymorphism in the apolipoprotein (a) gene on fibrinogen and Lp(a) levels, respectively.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available