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Coronary artery disease and polymorphisms in a receptor mediating shear stress-dependent platelet activation
M Murata1, Y Matsubara, K Kawano
1Department of Medicine, School of Medicine, Keio University, Tokyo, Japan.
Insights
Genetic variations in platelet glycoprotein (GP) Ib alpha may increase the risk of coronary artery disease (CAD) in younger individuals. The Met allele of GP Ib alpha is associated with both the prevalence and severity of CAD in those under 60.
Area of Science:
- Cardiovascular Genetics
- Platelet Biology
- Thrombosis Research
Background:
- Platelets are crucial in coronary thrombosis, with antiplatelet therapies common for coronary artery disease (CAD).
- Genetic factors influencing platelet function in CAD remain largely unexplored.
- The glycoprotein (GP) Ib/IX complex, a von Willebrand factor receptor, mediates platelet activation under shear stress.
Purpose of the Study:
- To investigate the association between genetic polymorphisms in the GP Ib alpha receptor and the prevalence and severity of CAD.
- To determine if specific GP Ib alpha genotypes are risk factors for CAD in different age groups.
Main Methods:
- Genotyping of GP Ib alpha (145Thr/Met polymorphism and variable number of tandem repeats) was performed.
- Study included 91 patients with confirmed CAD (myocardial infarction or angina) and 105 healthy controls.
- Coronary angiography was used to assess lesion severity (Gensini score).
Main Results:
- The Thr/Met genotype frequency was significantly higher in CAD patients under 60 years old compared to controls (31.8% vs. 16.0%).
- A significant association was found between the Thr/Met genotype and increased angiographic severity of CAD (Gensini score >= 40).
- No significant differences in GP Ib alpha genotype distribution were observed between myocardial infarction and angina pectoris patients.
Conclusions:
- The Met allele of GP Ib alpha appears to be a risk factor for CAD prevalence and severity in individuals aged 60 years or younger.
- Further large-scale studies with incident cases are recommended to validate these findings.
Background:
Platelets play pivotal roles in coronary thrombosis, and antiplatelet therapies are widely used for coronary artery disease (CAD). However, the effects of genetic variation in platelets on CAD are poorly understood. We have assessed the association between CAD and polymorphisms in a platelet receptor for von Willebrand factor, the glycoprotein (GP) Ib/IX complex, which mediates shear stress-dependent platelet activation.
Methods And Results:
Genotypes of the alpha-chain of the receptor (GP Ib alpha, 145Thr/Met) were determined in 91 patients with myocardial infarction (MI) or angina pectoris whose lesions were confirmed by coronary angiography as well as in 105 individuals from the general population with no history of angina or other heart diseases and normal resting ECGs. There was no homozygote for Met/Met in either the control or patient groups. The prevalence of the Thr/Met genotype (T/M) in all patients was not significantly different from that in the control group. However, the frequency of T/M was significantly higher in patients aged < or = 60 years (31.8%) than in control subjects aged < or = 60 years (16.0%; P<.05, odds ratio=2.5). An association was also demonstrated between CAD and the other polymorphism of GP Ib alpha, a variable number of tandem repeats of a 13-amino acid sequence, which is known to be linked to the 145Thr/Met polymorphism. There was an association between the frequency of the T/M genotype and the angiographic severity of CAD: 11.1% for Gensini score < 40 versus 50.0% for Gensini score > or = 40 (P=.0015). There was no difference in the distribution of GP Ib alpha genotypes between patients with MI and those with angina pectoris.
Conclusions:
This study suggests that the presence of the Met allele in GP Ib alpha is a risk factor for the prevalence and severity of CAD in individuals aged < or = 60 years. The results need to be confirmed in a large-scale study of incident case subjects and matching control subjects.