What diseases cause high ace levels
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Diseases and Genetic Mutations Causing High ACE Levels
Introduction to Angiotensin-Converting Enzyme (ACE)
Angiotensin-converting enzyme (ACE) is crucial in regulating blood pressure and vascular remodeling by metabolizing various peptides. Elevated ACE levels can be indicative of several diseases, particularly those involving cardiovascular and respiratory systems, as well as certain genetic mutations.
Genetic Mutations Leading to Elevated ACE Levels
Pro1199Leu Mutation
The Pro1199Leu mutation in the ACE gene has been identified as a significant cause of elevated ACE levels. This mutation enhances the cleavage-secretion process, leading to increased serum ACE. Families with this mutation, primarily of European descent, exhibit autosomal dominant hyper-ACE-emia without associated diseases .
Trp1197Stop Mutation
Another notable mutation is Trp1197Stop, which results in a truncated ACE protein lacking the transmembrane anchor, causing it to be secreted directly into the bloodstream. This mutation has been observed in families of African-American descent, leading to a dramatic 13-fold increase in serum ACE levels. Some carriers of this mutation may exhibit airflow obstruction or hypertension, although not all are affected.
IVS25+1G>A Splice-Site Mutation
The IVS25+1G>A splice-site mutation leads to the retention of intron 25 and the generation of a premature termination codon, resulting in a significant increase in circulating ACE levels. This mutation has been identified in Belgian families, with affected individuals showing no cardiovascular complications despite the elevated ACE levels.
Tyr465Asp Mutation
The Tyr465Asp (Y465D) mutation, located in the N domain of ACE, significantly increases the rate of ACE shedding, leading to elevated blood ACE levels. This mutation causes local conformational changes in ACE, enhancing its dimerization and accessibility for cleavage.
Diseases Associated with Elevated ACE Levels
Sarcoidosis
Sarcoidosis is a granulomatous disease where elevated serum ACE levels are commonly observed. This elevation is associated with the active disease process and can be used to monitor disease activity and response to therapy. Elevated ACE levels in sarcoidosis patients are significantly higher than in those with other chronic lung diseases.
Aortic Stenosis and COVID-19
Patients with severe aortic stenosis (AS) exhibit markedly elevated ACE2 levels, which is the receptor for SARS-CoV-2. This elevation correlates with altered ventricular functions and may increase susceptibility to severe COVID-19 outcomes in elderly patients with AS.
Familial Hyper-ACE-emia
Familial clustering of elevated ACE levels has been reported in several cases, often inherited as an autosomal dominant trait. These cases are characterized by significantly high serum ACE levels without associated diseases, suggesting a benign form of hyper-ACE-emia .
Conclusion
Elevated ACE levels can result from various genetic mutations and are associated with specific diseases such as sarcoidosis and aortic stenosis. Understanding these genetic and disease-related causes is crucial for accurate diagnosis and management of conditions involving elevated ACE levels.
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