(Circulation. 1997;96:3281-3286.)
© 1997 American Heart Association, Inc.
Articles |
Coronary Artery Disease and Polymorphisms in a Receptor Mediating Shear Stress–Dependent Platelet Activation
From the Department of Medicine, School of Medicine, Keio University (M.M., Y.M., T.Z., Y.I.), Tokyo; Second Department of Internal Medicine, Kyorin University (K.K., N.A., H.Y., K.I.), Tokyo; and Medical Center, Sakura Bank (G.W.), Tokyo, Japan.
Correspondence to Mitsuru Murata, MD, Department of Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160, Japan.
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 
-chain of the
receptor (GP Ib, 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 
60
years (31.8%) than in control subjects aged 60 years (16.0%;
P<.05, odds ratio=2.5). An association was also
demonstrated between CAD and the other polymorphism of GP Ib, 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 
40
(P=.0015). There was no difference in the distribution
of GP Ib genotypes between patients with MI and those with
angina pectoris.
Conclusions This study suggests that the presence of the Met
allele in GP Ib is a risk factor for the prevalence and severity
of CAD in individuals aged 60 years. The results need to be confirmed
in a large-scale study of incident case subjects and matching control
subjects.
Key Words: coronary disease • risk factors • platelets • glycoproteins • genetics
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