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Vascular and haemostatic gene polymorphisms associated with non-fatal myocardial infarction: a critical review
A Manzoli1, F Andreotti, A M Leone
1Department of Cardiovascular Sciences, University Campus Bio-Medico, Rome, Italy. a.manzoli@unicampus.it
Insights
Genetics play a role in myocardial infarction (MI), but conflicting results exist due to its complex, multigenic nature. Studying multiple gene variations and environmental factors together offers better insights into MI genetic risk.
Area of Science:
- Cardiovascular Genetics
- Molecular Cardiology
- Disease Pathogenesis
Background:
- Familial clustering suggests a genetic component in premature myocardial infarction (MI).
- Previous studies on gene polymorphisms in vascular and hemostatic factors have yielded inconsistent results regarding MI risk.
- The multigenic nature of MI and diverse pathogenetic mechanisms complicate the identification of individual gene contributions.
Purpose of the Study:
- To address the conflicting findings in genetic studies of myocardial infarction.
- To propose a more effective approach for understanding the genetic contribution to MI risk.
- To highlight the necessity of considering gene-gene and gene-environment interactions.
Main Methods:
- Review of existing literature on gene polymorphisms and myocardial infarction.
- Discussion of the limitations of single-gene polymorphism studies in complex diseases.
- Advocacy for simultaneous investigation of multiple polymorphisms and environmental factors.
Main Results:
- Single gene polymorphisms have a limited role in the overall risk of myocardial infarction.
- Myocardial infarction pathogenesis involves multiple genes and environmental influences.
- Conflicting results in prior studies are attributed to the disease's complexity.
Conclusions:
- A comprehensive approach is needed to unravel the genetic basis of myocardial infarction.
- Investigating sets of polymorphisms and their interactions with environmental factors is crucial.
- Understanding specific gene contributions requires studying homogeneous patient cohorts and multifactorial influences.
Abstract:
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.