Vascular and haemostatic gene polymorphisms associated with non-fatal myocardial infarction: a critical review.
The importance of genetics to the pathogenesis of myocardial infarction is suggested by the frequent familial clustering of premature disease. Yet, studies associating myocardial infarction with gene polymorphisms of vascular proteins (angiotensinogen, angiotensin converting enzyme, angiotensin II type 1 receptor, endothelial nitric oxide synthase) and haemostatic factors (fibrinogen, coagulation factors II, V, VII and XIII, plasminogen activator inhibitor-1, tissue-type plasminogen activator, platelet glycoproteins IIb/IIIa, Ia/IIa and Ib-IX-V, or methylenetetrahydrofolate reductase) have revealed conflicting results. This is hardly surprising, given: 1) the multigenic nature of myocardial infarction, whereby single polymorphisms are bound to play at best only a limited role in the global risk of disease; 2) the multiple pathogenetic mechanisms of infarction (e.g., atheromatous obstruction, plaque rupture, thrombosis, vasospasm), each of which is likely influenced by a number of genes and by several environmental factors. The simultaneous investigation of a set of polymorphisms--and of their interactions with environmental factors--in extremely homogeneous sets of patients should offer a better understanding of the contribution of specific genes to the risk of myocardial infarction.
Manzoli
A
A
Department of Cardiovascular Sciences, University Campus Bio-Medico, Rome, Italy. a.manzoli@unicampus.it
Andreotti
F
F
Leone
A M
AM
Sperti
G
G
Zecchi
P
P
Di Sciascio
G
G
D000808:Angiotensinogen / Q000235:genetics; D001779:Blood Coagulation Factors / Q000235:genetics*; D001792:Blood Platelets / Q000502:physiology; D005167:Factor VII / Q000235:genetics; D005340:Fibrinogen / Q000235:genetics; D005342:Fibrinolysis / Q000502:physiology; D006801:Humans; D009203:Myocardial Infarction / Q000235:genetics*; D019001:Nitric Oxide Synthase / Q000235:genetics; D052250:Nitric Oxide Synthase Type III; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D010980:Platelet Membrane Glycoproteins / Q000235:genetics; D011110:Polymorphism, Genetic; D011945:Receptors, Angiotensin / Q000235:genetics
D001779:Blood Coagulation Factors; D010980:Platelet Membrane Glycoproteins; D011945:Receptors, Angiotensin; D000808:Angiotensinogen; D005167:Factor VII; D005340:Fibrinogen; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D007703:Peptidyl-Dipeptidase A