title: Pharmacogenetic effects of angiotensin-converting enzyme inhibitors over age-related urea and creatinine variations in patients with dementia due to Alzheimer disease.
abstract: BACKGROUND
  Renal function declines according to age and vascular risk factors, whereas few data are available regarding genetically-mediated effects of anti-hypertensives over renal function.
  
  
  OBJECTIVE
  To estimate urea and creatinine variations in dementia due to Alzheimer disease (AD) by way of a pharmacogenetic analysis of the anti-hypertensive effects of angiotensin-converting enzyme inhibitors (ACEis).
  
  
  METHODS
  Consecutive outpatients older than 60 years-old with AD and no history of kidney transplant or dialytic therapy were recruited for prospective correlations regarding variations in fasting blood levels of urea and creatinine in one year, considering ACE genotypes of rs1800764 and rs4291 and their respective haplotypes, and treatment with ACEis along with blood pressure variations.
  
  
  RESULTS
  For 190 patients, 152 had arterial hypertension, and 122 used ACEis. Minor allele frequencies were 0.492 for rs1800764-C and 0.337 for rs4291-T, both in Hardy-Weinberg equilibrium. There were no overall significant yearly variations in levels of urea and creatinine, but their concurrent variations were positively correlated (ρ <0.0001). Each A allele of rs4291 led to an yearly urea increase of 3,074 mg/dL, and an yearly creatinine increase of 0.044 mg/dL, while the use of ACEis was protective regarding creatinine variations. The use of ACEis was also protective for carriers of rs1800764-CT/rs4291-AA, while carriers of rs1800764-CT/rs4291-AT had steeper reductions in creatinine levels, particularly when they were treated with ACEis.
  
  
  CONCLUSIONS
  Effects of ACEis over creatinine variations are genetically mediated and independent of blood pressure variations in older people with AD.
authors.affiliation: Department of Neurology and Neurosurgery, Escola Paulista de Medicina, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil.
authors.forename: Fabricio
authors.initials: F
authors.lastname: Ferreira de Oliveira
authors.affiliation: Department of Medicine, Escola Paulista de Medicina, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil.
authors.forename: Juliana Marília
authors.initials: JM
authors.lastname: Berretta
authors.affiliation: Department of Morphology and Genetics, Escola Paulista de Medicina, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Suchi Chen
authors.affiliation: Department of Morphology and Genetics, Escola Paulista de Medicina, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil.
authors.forename: Marilia
authors.initials: M
authors.lastname: Cardoso Smith
authors.affiliation: Department of Neurology and Neurosurgery, Escola Paulista de Medicina, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil.
authors.forename: Paulo Henrique
authors.initials: PH
authors.lastname: Ferreira Bertolucci
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000097:blood*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects / Q000235:genetics; D003404:Creatinine / Q000097:blood*; D005215:Fasting / Q000097:blood; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000235:genetics; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D014508:Urea / Q000097:blood*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D014508:Urea; D003404:Creatinine; D007703:Peptidyl-Dipeptidase A
keywords: Alzheimer disease; Renin-Angiotensin System; creatinine; pharmacogenetics; urea