title: Association of angiotensin-converting enzyme 2 (ACE2) gene polymorphisms with parameters of left ventricular hypertrophy in men. Results of the MONICA Augsburg echocardiographic substudy.
abstract: Angiotensin-converting enzyme (ACE) activity is considered to be of major importance for the conversion of angiotensin (Ang) I to Ang II. Recently, a second ACE, named ACE2, has been identified. Experimental data provide evidence that ACE2 might be involved in modulating cardiac structure and function. In the present explorative study, we assessed whether polymorphisms in the ACE2 gene are related to echocardiographically determined parameters of left ventricular mass, structure or function in the general population. Five intronic single nucleotide polymorphisms (SNPs) were genotyped using the 5'-exonuclease activity (TaqMan) assay in the echocardiographic substudy of the third MONICA Augsburg survey. As ACE2 is located on the X chromosome, women and men were analysed separately. Four SNPs showed high pairwise linkage disequilibrium (rs4646156, rs879922, rs4240157 and rs233575). The minor alleles of these four SNPs were associated with higher left ventricular mass index (LVMI) and higher septal wall thickness (SWT) in men. Likewise, male carriers of a common haplotype (frequency 29.9%) consisting of the minor alleles of these four SNPs displayed higher values for LVMI and SWT than non-carriers (LVMI: TGGC 98.8+/-1.52 vs non-TGGC 94.8+/-0.99 g/m(2), p=0.027; SWT: TGGC 11.5+/-0.14 vs non-TGGC 11.1+/-0.09 mm, p=0.019). Furthermore, this haplotype was associated with an increased odds ratio (OR) for left ventricular hypertrophy (OR 3.10, p=0.006). In women, similar but less pronounced and consistent trends were observed. No association was observed between any of these SNPs and parameters of left ventricular systolic or diastolic function nor with blood pressure levels. This study provides evidence that genetic variants in the ACE2 gene may be associated with left ventricular mass, SWT and left ventricular hypertrophy in hemizygous men.
authors.affiliation: Medizinische Klinik II, Universitätsklinikum Schleswig-Holstein, Ratzeburger Allee 160, 23538 Lübeck, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Lieb
authors.forename: Jochen
authors.initials: J
authors.lastname: Graf
authors.forename: Anika
authors.initials: A
authors.lastname: Götz
authors.forename: Inke R
authors.initials: IR
authors.lastname: König
authors.forename: Björn
authors.initials: B
authors.lastname: Mayer
authors.forename: Marcus
authors.initials: M
authors.lastname: Fischer
authors.forename: Jan
authors.initials: J
authors.lastname: Stritzke
authors.forename: Christian
authors.initials: C
authors.lastname: Hengstenberg
authors.forename: Stephan R
authors.initials: SR
authors.lastname: Holmer
authors.forename: Angela
authors.initials: A
authors.lastname: Döring
authors.forename: Hannelore
authors.initials: H
authors.lastname: Löwel
authors.forename: Heribert
authors.initials: H
authors.lastname: Schunkert
authors.forename: Jeanette
authors.initials: J
authors.lastname: Erdmann
mesh_terms: D000328:Adult; D000368:Aged; D000085962:Angiotensin-Converting Enzyme 2; D004452:Echocardiography; D005260:Female; D005838:Genotype; D006352:Heart Ventricles / Q000033:anatomy & histology / Q000473:pathology; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009929:Organ Size; D007703:Peptidyl-Dipeptidase A / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic; D012307:Risk Factors; D016276:Ventricular Function
chemical_list: D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2