title: Renal function dependent association of AGTR1 polymorphism (A1166C) and electrocardiographic left-ventricular hypertrophy.
abstract: BACKGROUND
  The association of renin-angiotensin system (RAS) polymorphisms and left-ventricular hypertrophy (LVH) may depend on the presence of risk factors for LVH, such as renal dysfunction. We studied whether renal function modulates the association between RAS polymorphisms and LVH in a cross-sectional study of 8592 inhabitants of Groningen.
  
  
  METHODS
  Left-ventricular hypertrophy was determined with electrocardiograms, using the Cornell voltage-duration product. The following RAS polymorphisms were determined: angiotensin II type-1 receptor (AGTR1 A1166C), angiotensin-converting enzyme (ACE) insertion/deletion (I/D), and angiotensinogen (AGT G-6A). The AGTR1 A1166C and ACE I/D polymorphisms were in Hardy-Weinberg equilibrium.
  
  
  RESULTS
  Electrocardiographic LVH was present in 417 (5.0%) subjects. Subjects with LVH were older (53 v 49 years) and overall had more cardiovascular risk factors. Using logistic regression, creatinine clearance interacted with the relationship between the AGTR1 A1166C polymorphism and LVH (beta, -0.19; P = .033). In subjects with the CC genotype, in contrast to carriers of an A allele, the prevalence of LVH increased with more pronounced renal dysfunction. Creatinine clearance also interacted with the relationship between the ACE I/D polymorphism and LVH (beta, 0.12; P = .037), although less strongly, and the other way around. Creatinine clearance did not influence the association between the AGT G-6A polymorphism and LVH (beta, -0.006; P = .491).
  
  
  CONCLUSIONS
  In this population-based study, the AGTR1 A1166C polymorphism was associated with LVH, dependent on concomitant renal dysfunction. A weaker renal function dependent association between the ACE I/D polymorphism and LVH was also observed. Renal function should be taken into account as a relevant environmental factor for the pathogenetic effects of RAS polymorphisms.
authors: Thorax Center, Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands. t.d.j.smilde@thorax.umcg.nl
authors: Tom D J
authors: TD
authors: Smilde
authors: Mike W
authors: MW
authors: Zuurman
authors: Hans L
authors: HL
authors: Hillege
authors: Dirk J
authors: DJ
authors: van Veldhuisen
authors: Wiek H
authors: WH
authors: van Gilst
authors: Gerrit
authors: G
authors: van der Steege
authors: Adriaan A
authors: AA
authors: Voors
authors: Jan A
authors: JA
authors: Kors
authors: Paul E
authors: PE
authors: de Jong
authors: Gerjan
authors: G
authors: Navis
mesh_terms: D000328:Adult; D000368:Aged; D003430:Cross-Sectional Studies; D004562:Electrocardiography; D005260:Female; D006720:Homozygote; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000235:genetics* / Q000503:physiopathology*; D007668:Kidney / Q000503:physiopathology*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000502:physiology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011446:Prospective Studies; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics* / Q000502:physiology; D012044:Regression Analysis; D012084:Renin-Angiotensin System / Q000235:genetics / Q000502:physiology; D012307:Risk Factors
chemical_list: D044140:Receptor, Angiotensin, Type 1; D007703:Peptidyl-Dipeptidase A