AGT and ACE genes influence classic mitral valve prolapse predisposition in Marfan patients.
BACKGROUND
In Marfan syndrome, the mitral valve prolapse, ranging from nonclassic to classic form on the basis of the leaflet thickness, is a common condition characterized by a highly variable structural abnormality. We investigated the role of angiotensinogen (AGT) M235T, angiotensin converting enzyme (ACE) I/D and angiotensin II type 1 receptor (AT1R) A1166C polymorphisms in influencing the susceptibility to classic or non-classic mitral valve prolapse in Marfan patients.


METHODS
We studied 135 Marfan patients with mitral valve prolapse, diagnosed by echocardiography. AGT, ACE, and AT1R polymorphisms were identified by polymerase chain reaction-based restriction analysis.


RESULTS
The frequency of the ACE D, but not AGT 235T and AT1R 1166C allele, was significantly higher in patients with classic mitral valve prolapse in comparison to that observed in the non-classic one (p=0.03). The percentage of subjects with the contemporaneous presence of ACE D and AGT 235T alleles was significantly higher in the classic mitral valve prolapse group in comparison to the non-classic one (79% vs. 55%, respectively; p=0.008). The concomitant presence of these two alleles was associated with increased susceptibility to the classic mitral valve prolapse (OR 3.02, p=0.016).


CONCLUSIONS
Our findings show a possible role of ACE and AGT genes as predisposing factors to classic mitral valve prolapse in Marfan patients, thus suggesting a role of renin angiotensin system genes in modulating mitral valve abnormality, and the need for an interventional study with angiotensin II type 1 receptor antagonists, which considers the leaflet thickness progression in Marfan patients with MVP.
Fatini
Cinzia
C
Department of Medical and Surgical Critical Care, University of Florence, Italy. cinziafatini@hotmail.com
Attanasio
Monica
M
Porciani
Cristina
C
Sticchi
Elena
E
Padeletti
Luigi
L
Lapini
Ilaria
I
Abbate
Rosanna
R
Gensini
Gian Franco
GF
Pepe
Guglielmina
G
D000293:Adolescent; D000328:Adult; D000483:Alleles; D000808:Angiotensinogen / Q000235:genetics*; D016022:Case-Control Studies; D018618:Echocardiography, Doppler, Color; D005260:Female; D005786:Gene Expression Regulation; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008382:Marfan Syndrome / Q000175:diagnosis / Q000235:genetics*; D008945:Mitral Valve Prolapse / Q000000981:diagnostic imaging / Q000235:genetics*; D016017:Odds Ratio; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D011336:Probability; D012016:Reference Values; D012680:Sensitivity and Specificity
D000808:Angiotensinogen; D007703:Peptidyl-Dipeptidase A