Genes, coagulation and cardiovascular risk

Coronary artery disease (CAD) is a multifactorial disease influenced by bot h genetic and environmental determinants, Coagulation activation plays a ke y role in thrombus formation and variation in its factors has been associat ed with the risk of CAD, The levels of these factors are genetically determ ined and polymorphisms in their genes can also be responsible for disease d evelopment. Three polymorphic alleles of coagulation factor VII (FVII) gene have been associated with a protective effect on the risk of familial myoc ardial infarction, Their distribution in Europe covaries across populations with the rate of myocardial infarction mortality, being higher in countrie s (like Italy, Spain, Greece) at low risk, These polymorphisms are major de terminants of FVII variability in humans. They can also determine the respo nse of FVII to environmental stimuli. Indeed, they modulate the association between triglycerides or smoking and FVII, while a gender-dependent regula tion of FVII, probably related to sexual hormones, has also been described. Interestingly, lowering the plasma levels of FVII with low dose warfarin t o the same low normal range as that associated with the 'protective' genoty pes, results in protection against ischaemic heart disease, reducing mortal ity in high risk men.