title: Association between the A1166C polymorphism of the angiotensin II receptor type 1 and progression of chronic renal insufficiency.
abstract: BACKGROUND
  In some studies genetic variation in the renin-angiotensin-aldosterone system (RAAS) has been associated with hypertension and rapid progression of renal insufficiency to end-stage renal disease (ESRD). Most of these studies do not take into account covariables influencing progression. We studied retrospectively the role of angiotensinogen (AGT) M235T, angiotensin converting enzyme (ACE) insertion/deletion (I/D), angiotensin II type 1 receptor (AT1R) A1166C, aldosterone syntase (CYP11B2) -344C/T and intron 2 W/C polymorphisms in conjunction with clinical and biochemical covariables on the rate of progression of renal insufficiency in a group of patients with ESRD of various etiologies.
  
  
  METHODS
  Genotyping was performed by polymerase chain reaction (PCR) in 104 ESRD patients (62 males and 42 females), aged 64 +/- 14 years (mean +/- SD) with mean initial serum creatinine of 2.6 +/- 1.1 mg/dL and a mean time to reach ESRD of 52 +/- 38 months.
  
  
  RESULTS
  The univariate analysis showed that there was a significant difference in the values of the slopes among the AT1R A1166C polymorphism genotypes: AA -4.87 +/- 0.22, AC -5.09 +/- 0.65 and CC -5.52 +/- 0.66 (p<0.05). None of the remainder polymorphisms showed significant association with progression. Stepwise multiple regression analysis including all the clinical, biochemical and genetic variables showed that only systolic blood pressure (SBP), serum PTHi and AT1R genotype were independently associated with the rate of progression, excluding the other variables from the model.
  
  
  CONCLUSIONS
  These results indicate that susceptibility to faster progression to ESRD is associated with the AT1R A1166C polymorphism. This association remains significant after adjustment for relevant covariates, highlighting the importance of analyzing genetic risk factors in the context of clinical and biochemical variables.
authors.affiliation: Nephrology Service, Institute of Biomedical Investigations, August Pi i Sunyer (IDIBAPS) Clinical Hospital, Barcelona, Spain.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Coll
authors.forename: Begoña
authors.initials: B
authors.lastname: Campos
authors.forename: Daniel
authors.initials: D
authors.lastname: González-Núñez
authors.forename: Albert
authors.initials: A
authors.lastname: Botey
authors.forename: Esteban
authors.initials: E
authors.lastname: Poch
mesh_terms: D000368:Aged; D001794:Blood Pressure; D018450:Disease Progression; D005260:Female; D005838:Genotype; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000235:genetics* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood; D011110:Polymorphism, Genetic; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000235:genetics*; D012189:Retrospective Studies
chemical_list: D010281:Parathyroid Hormone; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin