Association of the common genetic polymorphisms and haplotypes of the chymase gene with left ventricular mass in male patients with symptomatic aortic stenosis.
We investigated the association between polymorphisms and haplotypes of the chymase 1 gene (CMA1) and the left ventricular mass index (LVM/BSA) in a large cohort of patients with aortic stenosis (AS). Additionally, the gender differences in cardiac remodeling and hypertrophy were analyzed. The genetic background may affect the myocardial response to pressure overload. In human cardiac tissue, CMA1 is involved in angiotensin II production and TGF-β activation, which are two major players in the pathogenesis of hypertrophy and fibrosis. Preoperative echocardiographic data from 648 patients with significant symptomatic AS were used. The LVM/BSA was significantly lower (p<0.0001), but relative wall thickness (RWT) was significantly higher (p = 0.0009) in the women compared with the men. The haplotypes were reconstructed using six genotyped polymorphisms: rs5248, rs4519248, rs1956932, rs17184822, rs1956923, and rs1800875. The haplotype h1.ACAGGA was associated with higher LVM/BSA (p = 9.84 × 10(-5)), and the haplotype h2.ATAGAG was associated with lower LVM/BSA (p = 0.0061) in men, and no significant differences were found in women. Two polymorphisms within the promoter region of the CMA1 gene, namely rs1800875 (p = 0.0067) and rs1956923 (p = 0.0015), influenced the value of the LVM/BSA in males. The polymorphisms and haplotypes of the CMA1 locus are associated with cardiac hypertrophy in male patients with symptomatic AS. Appropriate methods for the indexation of heart dimensions revealed substantial sex-related differences in the myocardial response to pressure overload.
Department of Valvular Heart Diseases, Institute of Cardiology, Warsaw, Poland.
Ewa
E
Orlowska-Baranowska
Department of Internal Medicine, Hypertension, and Vascular Diseases, Medical University of Warsaw, Warsaw, Poland.
Jaroslaw
J
Gora
Clinic of Arrhythmia, Institute of Cardiology, Warsaw, Poland.
Rafal
R
Baranowski
Department of Valvular Heart Diseases, Institute of Cardiology, Warsaw, Poland.
Patrycjusz
P
Stoklosa
Department of Internal Medicine, Hypertension, and Vascular Diseases, Medical University of Warsaw, Warsaw, Poland.
Lucja
L
Gadomska vel Betka
Department of Internal Medicine, Hypertension, and Vascular Diseases, Medical University of Warsaw, Warsaw, Poland.
Ewa
E
Pedzich-Placha
Department of Valvular Heart Diseases, Institute of Cardiology, Warsaw, Poland.
Malogrzata
M
Milkowska
Faculty of Biology, University of Warsaw, Warsaw, Poland; Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland.
Marta K
MK
Koblowska
Department of Valvular Heart Diseases, Institute of Cardiology, Warsaw, Poland.
Tomasz
T
Hryniewiecki
Department of Internal Medicine, Hypertension, and Vascular Diseases, Medical University of Warsaw, Warsaw, Poland.
Zbigniew
Z
Gaciong
Department of Internal Medicine, Hypertension, and Vascular Diseases, Medical University of Warsaw, Warsaw, Poland.
Grzegorz
G
Placha
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001024:Aortic Valve Stenosis / Q000235:genetics* / Q000503:physiopathology; D053818:Chymases / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D006239:Haplotypes; D006352:Heart Ventricles / Q000503:physiopathology; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012737:Sex Factors; D055815:Young Adult
D053818:Chymases