RAAS gene polymorphisms influence progression of pediatric hypertrophic cardiomyopathy.
Hypertrophic Cardiomyopathy (HCM) is a disease with variable rate of progression. Young age is an independent risk factor for poor outcome in HCM. The influence of renin-angiotensin-aldosterone (RAAS) genotype on the progression of HCM in children is unknown. Children with HCM (n = 65) were enrolled prospectively across two centers (2001-2005). All subjects were genotyped for five RAAS gene polymorphisms previously associated with LV hypertrophy (pro-LVH): AGT M235T, ACE DD, CMA-1903 A/G, AGTR1 1666 A/C and CYP11B2-344 C/T. Linear regression models, based on maximum likelihood estimates, were created to assess the independent effect of RAAS genotype on LV hypertrophy (LVH). Forty-six subjects were homozygous for <2 and 19 were homozygous for > or =2 pro-LVH RAAS polymorphisms. Mean age at presentation was 9.6 +/- 6 years. Forty children had follow-up echocardiograms after a median of 1.5 years. Indexed LV mass (LVMI) and LV mass z-scores were higher at presentation and follow-up in subjects with > or =2 pro-LVH genotypes compared to those with <2 (P < 0.05). Subjects with > or =2 pro-LVH genotypes also demonstrated a greater increase in septal thickness (IVST) and in LV outflow tract (LVOT) obstruction on follow-up (P < 0.05). On multivariate analysis, a higher number of pro-LVH genotypes was associated with a larger effect size (P < 0.05). Pro-LVH RAAS gene polymorphisms are associated with progressive septal hypertrophy and LVOT obstruction in children with HCM. Identification of RAAS modifier genes may help to risk-stratify patients with HCM.
Kaufman
Beth D
BD
Department of Pediatrics, Columbia University, New York, NY, 10032, USA.
Auerbach
Scott
S
Reddy
Sushma
S
Manlhiot
Cedric
C
Deng
Liyong
L
Prakash
Ashwin
A
Printz
Beth F
BF
Gruber
Dorota
D
Papavassiliou
Dimitrios P
DP
Hsu
Daphne T
DT
Sehnert
Amy J
AJ
Chung
Wendy K
WK
Mital
Seema
S
D000293:Adolescent; D000328:Adult; D000483:Alleles; D001483:Base Sequence; D024741:Cardiomyopathy, Hypertrophic, Familial / Q000000981:diagnostic imaging / Q000209:etiology / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D017931:DNA Primers / Q000235:genetics; D015150:Echocardiography, Doppler; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000000981:diagnostic imaging / Q000209:etiology / Q000235:genetics; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D010641:Phenotype; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012084:Renin-Angiotensin System / Q000235:genetics*
D017931:DNA Primers