RAAS gene polymorphisms influence progression of pediatric hypertrophic cardiomyopathy

Beth D. Kaufman, Scott Auerbach, Sushma Reddy, Cedric Manlhiot, Liyong Deng, Ashwin Prakash, Beth F. Printz, Dorota Gruber, Dimitrios P. Papavassiliou, Daphne T. Hsu, Amy J. Sehnert, Wendy K. Chung, Seema Mital

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


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, AGTR11666 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 ≥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 ≥2 pro-LVH genotypes compared to those with <2 (P < 0.05). Subjects with <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.

Original languageEnglish (US)
Pages (from-to)515-523
Number of pages9
JournalHuman genetics
Issue number5
StatePublished - Dec 2007
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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