Is ACE level rather than ACE genotype a risk factor for cardiovascular disease?
(English)Manuscript (preprint) (Other academic)
Background: Polymorphism in the angiotensin-converting enzyme gene (ACE I/D polymorphism) is associated with the level of ACE in plasma. However, there are large variations in plasma ACE level among individuals with the same genotype. Furthermore, ACE D/D genotype has been associated with increased risk for cardiovascular disease. The aim of this study was to investigate variations in plasma ACE levels in order to elucidate the associations between circulating ACE levels, ACE genotype, known cardiovascular risk factors and cardiovascular diseases (CVDs).
Methods and Results: Plasma ACE levels and ACE genotype were analysed in a Swedish population consisting of 672 elderly men and women. Association between ACE-genotype, levels of circulating ACE and known cardiovascular risk factors and CVDs were analyzed. The results showed increased plasma ACE levels in individuals with hypertension (p=0.003), ischemic heart disease (p=0.03), in smokers (p=0.011) and in individuals with heredity for CVDs (p=0.031). Furthermore, treatment with ACE inhibitors increased the level of ACE in plasma (p<0.001). No association was found between D/D genotype and CVD. Instead, ischemic heart disease was more frequent among carriers of the I/I genotype (p=0.009).
Conclusion: Although plasma ACE levels are strongly influenced by ACE genotype, there are large variations in plasma ACE level among carriers of the same genotype. Our data does not support an association between ACE D/D polymorphism and CVDs but indicates an association to increased level of ACE in the circulation, suggesting that ACE level rather than ACE genotype is the crucial factor associated with risk for CVDs.
Atherosclerosis, endothelium, genetics, hypertension, smoking
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-16703OAI: oai:DiVA.org:liu-16703DiVA: diva2:160222