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Genes, coagulation and cardiovascular risk
M B Donati1, F Zito, A D Castelnuovo
1Angela Valenti Laboratory of Genetic and Environmental Risk Factors for Thrombotic Disease, Department of Vascular Medicine and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri, Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy.
Insights
Genetic variations in coagulation factor VII (FVII) influence coronary artery disease (CAD) risk. Specific FVII gene polymorphisms offer protection against myocardial infarction, impacting disease rates across Europe.
Area of Science:
- Cardiovascular Genetics
- Hemostasis and Thrombosis
Background:
- Coronary artery disease (CAD) is multifactorial, involving genetic and environmental factors.
- Coagulation activation is crucial in thrombus formation, with factor variations linked to CAD risk.
- Genetic polymorphisms in coagulation factor genes contribute to disease development.
Purpose of the Study:
- Investigate the association between coagulation factor VII (FVII) gene polymorphisms and the risk of familial myocardial infarction.
- Examine the geographical distribution of these polymorphisms in relation to myocardial infarction mortality rates.
- Explore how these polymorphisms influence FVII levels and their response to environmental factors.
Main Methods:
- Analysis of three polymorphic alleles in the coagulation factor VII (FVII) gene.
- Correlation of allele distribution with myocardial infarction mortality rates across European populations.
- Assessment of FVII modulation by environmental factors like triglycerides and smoking.
- Investigation of gender-dependent regulation of FVII levels.
Main Results:
- Three FVII gene polymorphisms are associated with a protective effect against familial myocardial infarction.
- The prevalence of these protective polymorphisms inversely correlates with myocardial infarction mortality across Europe.
- These polymorphisms are key determinants of human FVII variability and modulate FVII response to environmental factors.
- A gender-dependent regulation of FVII, possibly linked to sex hormones, was observed.
Conclusions:
- FVII gene polymorphisms play a significant role in determining CAD risk and myocardial infarction incidence.
- Understanding these genetic factors can inform population-level risk assessment and prevention strategies.
- Therapeutic strategies, such as lowering FVII levels with warfarin, may mimic the protective effects of favorable genotypes.
Abstract:
Coronary artery disease (CAD) is a multifactorial disease influenced by both genetic and environmental determinants. Coagulation activation plays a key role in thrombus formation and variation in its factors has been associated with the risk of CAD. The levels of these factors are genetically determined and polymorphisms in their genes can also be responsible for disease development. Three polymorphic alleles of coagulation factor VII (FVII) gene have been associated with a protective effect on the risk of familial myocardial infarction. Their distribution in Europe covaries across populations with the rate of myocardial infarction mortality, being higher in countries (like Italy, Spain, Greece) at low risk. These polymorphisms are major determinants of FVII variability in humans. They can also determine the response of FVII to environmental stimuli. Indeed, they modulate the association between triglycerides or smoking and FVII, while a gender-dependent regulation of FVII, probably related to sexual hormones, has also been described. Interestingly, lowering the plasma levels of FVII with low dose warfarin to the same low normal range as that associated with the 'protective' genotypes, results in protection against ischaemic heart disease, reducing mortality in high risk men. Journal of Human Hypertension (2000) 14, 369-372