Genes, coagulation and cardiovascular risk.
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
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Angela 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.
Zito
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Castelnuovo
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Iacoviello
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D002318:Cardiovascular Diseases / Q000235:genetics*; D005167:Factor VII / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D009203:Myocardial Infarction / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D018570:Risk Assessment; D012680:Sensitivity and Specificity
D005167:Factor VII