title: Role of candidate modifier genes on the phenotypic expression of hypertrophy in patients with hypertrophic cardiomyopathy.
abstract: BACKGROUND
  The phenotypic expression of left ventricular hypertrophy (LVH) in patients with hypertrophic cardiomyopathy (HCM) is variable. This phenotypic variability is not completely explained by the responsible mutations or other known factors. Recent data denote a role for the modifier genes and environmental factors. We studied the role of 3 potential modifier genes, i.e., angiotensinogen (AGT), angiotensin II receptor 1a (AT1a), and endothelin-1 (END1) on the phenotypic expression of LVH in patients with hypertrophic cardiomyopathy (HCM).
  
  
  METHODS
  The study population was comprised of 108 genetically independent patients with HCM. Left ventricular mass index (LVMI) and LVH score were determined per published protocols. The genotypes of AGT (M235T, T174M, and G-6A), AT1a, and END1 were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or mutation-specific PCR (MS-PCR).
  
  
  RESULTS
  Male patients had higher mean LVMI and LVH score than female patients (146.0 +/- 33.5 vs 129.4 +/- 33.6, p = 0.01 and 6.0 vs 5.0, p = 0.010, respectively). Gender accounted for 4.8% and 5.4% of the variability of LVMI and LVH score, respectively. The END1 genotypes also had a significant influence on LVH scores accounting for 2.9% of their variability (p = 0.042). The median LVH score was greater in patients with the AA and AG genotypes, as compared to patients with the GG genotype (7.0 vs 5.0, p = 0.034). Neither the AGT nor the AT1 genotypes had a significant influence on the expression of LVH. In multivariate regression analysis, END1 and gender accounted for 7.3% of the variability of the LVH score (p = 0.007).
  
  
  CONCLUSIONS
  Our results show that gender and the END1 gene modify the phenotypic expression of hypertrophy in patients with HCM.
authors.affiliation: Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: R
authors.initials: R
authors.lastname: Brugada
authors.forename: W
authors.initials: W
authors.lastname: Kelsey
authors.forename: M
authors.initials: M
authors.lastname: Lechin
authors.forename: G
authors.initials: G
authors.lastname: Zhao
authors.forename: Q T
authors.initials: QT
authors.lastname: Yu
authors.forename: W
authors.initials: W
authors.lastname: Zoghbi
authors.forename: M
authors.initials: M
authors.lastname: Quinones
authors.forename: E
authors.initials: E
authors.lastname: Elstein
authors.forename: A
authors.initials: A
authors.lastname: Omran
authors.forename: H
authors.initials: H
authors.lastname: Rakowski
authors.forename: D
authors.initials: D
authors.lastname: Wigle
authors.forename: C C
authors.initials: CC
authors.lastname: Liew
authors.forename: M
authors.initials: M
authors.lastname: Sole
authors.forename: R
authors.initials: R
authors.lastname: Roberts
authors.forename: A J
authors.initials: AJ
authors.lastname: Marian
mesh_terms: D000328:Adult; D000808:Angiotensinogen / Q000235:genetics*; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics* / Q000473:pathology; D017931:DNA Primers / Q000737:chemistry; D019332:Endothelin-1 / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D005838:Genotype; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011945:Receptors, Angiotensin / Q000235:genetics*; D012727:Sex Characteristics
chemical_list: D017931:DNA Primers; D019332:Endothelin-1; D011945:Receptors, Angiotensin; D000808:Angiotensinogen