title: Association of ACE2 genetic variants with blood pressure, left ventricular mass, and cardiac function in Caucasians with type 2 diabetes.
abstract: BACKGROUND
  Cardiovascular disease is common in diabetes, and is associated with activation of the renin-angiotensin system (RAS). Angiotensin-converting enzyme (ACE)2 is a recently described member of the RAS, and this study investigated whether ACE2 polymorphisms are associated with hypertension, left ventricular (LV) mass, and cardiac function in type 2 diabetes.
  
  
  METHODS
  Variants in ACE2 (rs1978124, rs2074192, rs4240157, rs4646156, rs4646188) were examined in 503 Caucasian subjects with type 2 diabetes. As ACE2 is located on the X chromosome, analyses were performed separately for men and women. Hypertension was defined by a history of hypertension, and/or antihypertensive medications or blood pressure (BP) >130/80 mm Hg. LV mass and systolic function (ejection fraction) were assessed by transthoracic echocardiography.
  
  
  RESULTS
  In men, hypertension was more prevalent with the ACE2 rs2074192 C allele (P = 0.023), rs4240157 G allele (P = 0.016) and rs4646188 T allele (P = 0.006). In men, the rs1978124 A allele was associated with a significantly lower ejection fraction compared to the G allele (62.3 ± 13.3 vs. 67.2 ± 10.9%, P = 0.002). This association remained significant after covariate adjustment for age, body mass index, hypertension, antihypertensive treatment, and BP. In women, the prevalence of hypertension was higher (P = 0.009) with the rs4240157 G allele, and the rs1978124 A allele was associated with significantly higher LV mass (P = 0.008).
  
  
  CONCLUSIONS
  In Caucasians with type 2 diabetes, genetic variation in ACE2 is associated with hypertension and reduced systolic function in men, and hypertension and increased LV mass in women.
authors: Department of Medicine, University of Melbourne, Austin Health, Victoria, Australia. skpatel@unimelb.edu.au
authors: Sheila K
authors: SK
authors: Patel
authors: Bryan
authors: B
authors: Wai
authors: Michelle
authors: M
authors: Ord
authors: Richard J
authors: RJ
authors: MacIsaac
authors: Sharon
authors: S
authors: Grant
authors: Elena
authors: E
authors: Velkoska
authors: Sianna
authors: S
authors: Panagiotopoulos
authors: George
authors: G
authors: Jerums
authors: Piyush M
authors: PM
authors: Srivastava
authors: Louise M
authors: LM
authors: Burrell
mesh_terms: D000328:Adult; D000368:Aged; D000085962:Angiotensin-Converting Enzyme 2; D001794:Blood Pressure / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000453:epidemiology / Q000503:physiopathology*; D005260:Female; D056726:Genetic Association Studies; D014644:Genetic Variation; D006321:Heart / Q000503:physiopathology; D006801:Humans; D006973:Hypertension / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D015995:Prevalence; D013318:Stroke Volume / Q000235:genetics; D014463:Ultrasonography; D044465:White People / Q000235:genetics* / Q000706:statistics & numerical data
chemical_list: D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2