ACE and PAI-1 Gene Variants and Mortality.

Studies have reported conflicting results regarding the association of ACE and PAI-1 gene variants with myocardial infarction and ischemic heart disease.

While some studies have reported an association of the ACE D/D genotype with a history of myocardial infarction, most larger studies have found no evidence for an association with myocardial infarction or ischemic heart disease.

Our observation that the ACE D/D genotype was not associated with mortality or fatal cardiovascular disease in old age indicates that the overall effect of the ACE polymorphisms on fatal disease is probably limited.

The current study could not provide an explanation for the gender-specificity of the association with fatal ischemic heart disease. One previous study also reported data on both genders separately, and these showed that the PAI-1 4G/4G genotype was a risk factor for myocardial infarction in men only.

Interaction.

Recent studies showed that the PAI-1 4G/4G as well as the ACE D/D genotype is associated with increased PAI-1 levels. Although the possible deleterious effect on mortality of a decreased fibrinolytic capacity might have been more readily observed in subjects carrying both risk genotypes, none of our analyses indicated an increased mortality in this subgroup.

PAI-1 4G/5G polymorphism.

We found that men 85 years old carrying the PAI-1 4G/4G genotype were at a threefold increased risk of death due to ischemic heart disease during a 10-year follow-up period. This was not reflected in the risk of death from all cardiovascular causes combined or increased mortality before the age of 85 years. The indication that the PAI-1 polymorphism may contribute to the development ofThis text appears to be a list of references for various studies related to genetic factors and their association with myocardial infarction. No processing is required for this text.Geneva, Switzerland: World Health Organization. 

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