title: Endothelin-1 and vasopressin plasma levels are not associated with the insertion/deletion polymorphism of the human angiotensin I-converting enzyme gene in patients with coronary artery disease.
abstract: The objective was to investigate whether the renin-angiotensin (RA) system and related peptides endothelin-1 (ET-1) and vasopressin (VP) influence the development of coronary artery disease (CAD). Angiotensin I-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism has been associated with the risk of CAD. The ACE I/D polymorphism determines ACE activity, but plasma levels of other RA system components remain unchanged. However, ET-1 and VP production could be increased by RA system-dependent stimulation, continually promoted by paracrine stimulation and sustained by neointimal growth. ET-1 and VP have not been associated with the ACE I/D polymorphism so far. The present study investigated the association of the ACE I/D polymorphism with plasma concentrations of ET-1 and VP, as well as with renin, angiotensin-II (AT-II) and ACE activity in 98 Caucasian individuals with CAD. ACE I/D polymorphism showed no association with plasma levels of VP, ET-1, AT-II or renin. These parameters were also not associated taking into consideration different patient variables, such as diabetes mellitus, hypertension or severity of CAD. Only plasma ACE activity was associated with the D allele. In conclusion, the ACE I/D polymorphism could not be related to plasma concentrations of VP, ET-1, renin or AT-II, but as previously demonstrated, it could only be related to ACE activity in patients with CAD. Differences in ACE activity between ACE I/D genotype subgroups are probably compensated within the RA system itself or within non-ACE pathways, so that plasma concentrations of the related peptides ET-1 and VP remain unaffected.
authors.affiliation: Instritute of Clinical Chemistry and Pathobiochemistry, Justus Liebig University, Gaffkystrasse 11, 35392 Giessen, Germany. nadia.al-fakhri@klinchemie.med.uni-giessen.de
authors.forename: N
authors.initials: N
authors.lastname: Al-Fakhri
authors.forename: R E
authors.initials: RE
authors.lastname: Linhart
authors.forename: M
authors.initials: M
authors.lastname: Philipp
authors.forename: M
authors.initials: M
authors.lastname: Heidt
authors.forename: F W
authors.initials: FW
authors.lastname: Hehrlein
authors.forename: A
authors.initials: A
authors.lastname: Gardemann
authors.forename: N
authors.initials: N
authors.lastname: Katz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000804:Angiotensin II / Q000097:blood / Q000235:genetics; D003324:Coronary Artery Disease / Q000097:blood* / Q000235:genetics*; D019332:Endothelin-1 / Q000097:blood* / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D006801:Humans; D008297:Male; D008875:Middle Aged; D016254:Mutagenesis, Insertional / Q000235:genetics*; D007703:Peptidyl-Dipeptidase A / Q000097:blood* / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D012083:Renin / Q000097:blood / Q000235:genetics; D014662:Vasoconstrictor Agents / Q000097:blood*; D014667:Vasopressins / Q000097:blood*
chemical_list: D019332:Endothelin-1; D014662:Vasoconstrictor Agents; D014667:Vasopressins; D000804:Angiotensin II; D007703:Peptidyl-Dipeptidase A; D012083:Renin