Genetic polymorphisms and risk of coronary artery disease. 1998

M Murata, and K Kawano, and Y Matsubara, and K Ishikawa, and K Watanabe, and Y Ikeda
Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.

The fact that certain ethnic groups and specific populations residing in certain geographic areas carry an increased risk for thrombosis and that thrombosis occurs in young patients without established risk factors indicates the presence of new, previously unrecognized inherited conditions predisposing to thrombosis. We are now aware that interindividual variations within the loci coding for proteins relevant to lipid and vascular metabolisms as well as blood coagulation are universally found. Platelets play central roles in cerebrovascular diseases and acute coronary syndromes, as demonstrated by histopathological findings and clinical observations showing the efficacy of antiplatelet therapies for these disorders. In this article, we show our recent findings on the association between coronary artery disease (CAD) and polymorphisms in platelet membrane glycoproteins. The glycoprotein (GP) Ib/IX complex is a receptor for von Willebrand factor, which mediates shear stress-dependent platelet activation. It has recently been implicated in the pathogenesis of acute coronary syndromes. We have determined genotypes of the "size-polymorphism" of GPIb alpha--i.e., the variable number (1-4) of a 13 amino acid sequence (399-411)--in angiographically proven Japanese CAD patients with myocardial infarction or angina pectoris as well as in individuals from the general population with no history of angina or other heart diseases and normal resting electrocardiograms (ECG). We have found that the genotypes having at least one 4-repeat allele (4R) are more frequently found in patients than in controls. Logistic regression analyses for the adjustment of age, sex, and other acquired coronary risk factors provided an odds ratio of 7.94 (p=0.0043) for those with 4R vs. those without 4R, suggesting that the presence of 4R is an independent risk factor for CAD. The molecular mechanisms underlying this association are currently under investigation. Relationships between arterial thrombosis and polymorphisms in other platelet GPs (collagen receptor and fibrinogen receptor), blood coagulation factors, fibrinolytic factors, vasoactive substances, and factors relevant for lipid metabolisms are also discussed.

UI MeSH Term Description Entries
D007564 Japan A country in eastern Asia, island chain between the North Pacific Ocean and the Sea of Japan, east of the Korean Peninsula. The capital is Tokyo. Bonin Islands
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D011110 Polymorphism, Genetic The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level. Gene Polymorphism,Genetic Polymorphism,Polymorphism (Genetics),Genetic Polymorphisms,Gene Polymorphisms,Polymorphism, Gene,Polymorphisms (Genetics),Polymorphisms, Gene,Polymorphisms, Genetic
D001792 Blood Platelets Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. Platelets,Thrombocytes,Blood Platelet,Platelet,Platelet, Blood,Platelets, Blood,Thrombocyte
D003327 Coronary Disease An imbalance between myocardial functional requirements and the capacity of the CORONARY VESSELS to supply sufficient blood flow. It is a form of MYOCARDIAL ISCHEMIA (insufficient blood supply to the heart muscle) caused by a decreased capacity of the coronary vessels. Coronary Heart Disease,Coronary Diseases,Coronary Heart Diseases,Disease, Coronary,Disease, Coronary Heart,Diseases, Coronary,Diseases, Coronary Heart,Heart Disease, Coronary,Heart Diseases, Coronary
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D000368 Aged A person 65 years of age or older. For a person older than 79 years, AGED, 80 AND OVER is available. Elderly
D012307 Risk Factors An aspect of personal behavior or lifestyle, environmental exposure, inborn or inherited characteristic, which, based on epidemiological evidence, is known to be associated with a health-related condition considered important to prevent. Health Correlates,Risk Factor Scores,Risk Scores,Social Risk Factors,Population at Risk,Populations at Risk,Correlates, Health,Factor, Risk,Factor, Social Risk,Factors, Social Risk,Risk Factor,Risk Factor Score,Risk Factor, Social,Risk Factors, Social,Risk Score,Score, Risk,Score, Risk Factor,Social Risk Factor
D019038 Platelet Glycoprotein GPIb-IX Complex Platelet membrane glycoprotein complex essential for normal platelet adhesion and clot formation at sites of vascular injury. It is composed of three polypeptides, GPIb alpha, GPIb beta, and GPIX. Glycoprotein Ib functions as a receptor for von Willebrand factor and for thrombin. Congenital deficiency of the GPIb-IX complex results in Bernard-Soulier syndrome. The platelet glycoprotein GPV associates with GPIb-IX and is also absent in Bernard-Soulier syndrome. Antigens, CD42a,Antigens, CD42b,Antigens, CD42c,Antigens, CD42d,CD42a Antigens,CD42b Antigens,CD42c Antigens,CD42d Antigens,Platelet Membrane Glycoprotein IX,Platelet Membrane Glycoprotein Ib,Platelet Membrane Glycoprotein V,CD42a Antigen,CD42b Antigen,CD42c Antigen,CD42d Antigen,Glycoprotein Ib,Glycoprotein Ib alpha,Glycoprotein Ib beta,Glycoprotein Ib-IX Complex,Platelet Glycoprotein IX,Antigen, CD42a,Antigen, CD42b,Antigen, CD42c,Antigen, CD42d,Glycoprotein Ib IX Complex,Platelet Glycoprotein GPIb IX Complex

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