title: Polymorphisms of angiotensin-converting enzyme 2 gene associated with magnitude of left ventricular hypertrophy in male patients with hypertrophic cardiomyopathy.
abstract: BACKGROUND
  Even carrying an identical gene mutation, inter- and intra-family variations have been noticed worldwide in the presence and the severity of left ventricular hypertrophy and sudden death in patients with hypertrophic cardiomyopathy (HCM). Modifier genes may contribute to the diversity. Angiotensin-converting enzyme 2 (ACE2) gene has been established to be associated with parameters of left ventricular hypertrophy in community based male subjects. The objective of the present study was to investigate the association of ACE2 gene polymorphisms with the phenotype of HCM.
  
  
  METHODS
  A total of 261 consecutive HCM patients and 609 healthy controls were enrolled into this study. The polymorphism of rs2106809 and rs6632677 were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and confirmed by sequencing. Logistic regression model and multivariate analysis were used to determine the odds ratio (OR) and 95% confidence intervals (CI) of variations of ACE2 for HCM.
  
  
  RESULTS
  The T allele of rs2106809 and C allele of rs6632677 conferred increasing risk for HCM (OR 1.34, 95% CI 1.01 - 1.77, P = 0.04; OR 1.11, 95% CI 1.03 - 1.21, P = 0.002, respectively), and the 2 single nucleotide polymorphisms (SNPs) were in strong linkage disequilibrium (LD), the TC haplotype was independently associated with a higher OR for HCM (OR = 1.59, 95% CI 1.21 - 1.87) after adjusted for conventional risk factors. And the risk alleles were associated with thicker interventricular septal thickness of HCM ((20.0 +/- 6.3) mm vs (17.9 +/- 5.5) mm, P = 0.03 and (21.3 +/- 5.9) mm vs (17.9 +/- 5.8) mm, P = 0.04, respectively). No association was found between the two polymorphisms with female patients with HCM.
  
  
  CONCLUSIONS
  Minor alleles of ACE2 gene might be the genetic modifier for the magnitude of left ventricular hypertrophy in male patients with HCM.
authors.affiliation: Department of Cardiology, Fuwai Hospital and Cardiovascular Institute, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100037, China.
authors.forename: Shu-xia
authors.initials: SX
authors.lastname: Wang
authors.forename: Chun-yan
authors.initials: CY
authors.lastname: Fu
authors.forename: Yu-bao
authors.initials: YB
authors.lastname: Zou
authors.forename: Hu
authors.initials: H
authors.lastname: Wang
authors.forename: Yi
authors.initials: Y
authors.lastname: Shi
authors.forename: Xi-qi
authors.initials: XQ
authors.lastname: Xu
authors.forename: Jing-zhou
authors.initials: JZ
authors.lastname: Chen
authors.forename: Xiao-dong
authors.initials: XD
authors.lastname: Song
authors.forename: Tu-jun
authors.initials: TJ
authors.lastname: Huan
authors.forename: Ru-tai
authors.initials: RT
authors.lastname: Hui
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000085962:Angiotensin-Converting Enzyme 2; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics*; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D012737:Sex Factors
chemical_list: D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2