title: Effect of genetic variation on therapy with angiotensin converting enzyme inhibitors or angiotensin receptor blockers in dialysis patients.
abstract: BACKGROUND
  The role of interaction of polymorphisms in the Renin-Angiotensin-System (RAS) with angiotensin converting enzyme (ACE) or angiotensin receptor (AGTR1) inhibitors (RAS inhibitors) is unknown, as is the role of such therapy in end stage renal disease (ESRD) patients.
  
  
  METHODS
  We enrolled all 445 prevalent patients with diabetic nephropathy receiving maintenance hemodialysis in 30 centers in Southern Germany from August 1999 to January 2000 for prospective survival analysis until December 2003. Blood pressure and medication was recorded at inclusion. We determined survival specific for allelic variants of the ACE (insertion/deletion), Angiotensinogen (M235T) and AGTR1 (A1166C) genes. The effect of therapy with RAS inhibitors at study inclusion was determined for the allelic variants of each gene. The primary end point was all cause mortality (ACM).
  
  
  RESULTS
  For all polymorphisms, and for therapy with RAS inhibitors there was no significant effect on survival in the complete collective (n = 445), though there was an insignificant trend for improved survival in patients on AGTR1 antagonists. Increased ACM risk was associated with treatment with RAS inhibitors only in patients homozygous for the wild type AGTR1 1166A allele (HR 1.65, p = 0.01). For all other polymorphisms, therapy with RAS inhibitors had no significant effect on ACM, irrespective of genotype. Similar results were obtained in patients with systolic ventricular dysfunction.
  
  
  CONCLUSIONS
  Our data do not show a survival advantage for type 2 diabetes hemodialysis patients receiving RAS inhibiting therapy. In addition, our data indicate that allelic variation in RAS genes and pharmacogenetic interaction with RAS inhibition does not affect mortality risk in diabetic hemodialysis patients.
authors.affiliation: Klinik und Poliklinik für Innere Medizin II, Klinikum der Universität of Regensburg, Franz-Josef-Strauss-Allee 11, D-93053 Regensburg, Germany. carsten.boeger@klinik.uni-regensburg.de
authors.forename: C A
authors.initials: CA
authors.lastname: Böger
authors.forename: A K
authors.initials: AK
authors.lastname: Götz
authors.forename: B
authors.initials: B
authors.lastname: Krüger
authors.forename: M
authors.initials: M
authors.lastname: Hösl
authors.forename: G
authors.initials: G
authors.lastname: Schmitz
authors.forename: G A J
authors.initials: GA
authors.lastname: Riegger
authors.forename: B K
authors.initials: BK
authors.lastname: Krämer
mesh_terms: D000368:Aged; D000483:Alleles; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000808:Angiotensinogen / Q000235:genetics; D001794:Blood Pressure / Q000187:drug effects; D002908:Chronic Disease; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000209:etiology*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D011446:Prospective Studies; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics*; D006435:Renal Dialysis; D012084:Renin-Angiotensin System / Q000235:genetics*; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D044140:Receptor, Angiotensin, Type 1; D000808:Angiotensinogen; D007703:Peptidyl-Dipeptidase A