title: Progression of chronic kidney disease: Adrenergic genetic influence on glomerular filtration rate decline in hypertensive nephrosclerosis.
abstract: BACKGROUND
  African-Americans are likely to develop hypertension and hypertensive nephrosclerosis. This grave prognosis, coupled with familial aggregation of end-stage renal disease (ESRD) in Blacks, prompts a search for genetic risk factors for ESRD. Recent evidence implicates a crucial role for the sympathetic nervous system in progressive renal disease.
  
  
  METHODS
  We used the African-American Study of Kidney Disease to probe whether beta2-adrenergic receptor (ADRB2) predicts glomerular filtration rate (GFR) decline rate. A total of 580 participants were included. Baseline GFR was 51.2 +/- 0.5 ml/min/1.73 m2. Subjects were randomized in a 2 x 3 block design: to intensively lowered (MAP < or = 92 mm Hg) versus 'usual' (MAP = 102-107 mm Hg) blood pressure goal groups, and also divided by three randomized antihypertensive drugs (ramipril, metoprolol, or amlodipine). We scored 4 SNPs at the ADRB2 locus.
  
  
  RESULTS
  Haplotypes at ADRB2 predicted chronic GFR decline rate, GFR declined more slowly in individuals with haplotype-1 (-804G-->173T-->16Gly-->27GIn), and faster in those who carried haplotype-3 (-804G-->173T-->16Arg-->27Gln). ADRB2 genotype interacted with antihypertensive drug class to influence GFR slope (p = 0.001-0.037). We extended our findings to an independent case/control sample of Black hypertensive ESRD, in which we found that variant Gly16Arg that tagged the GFR slope-determining ADRB2 haplotype also conferred risk for the ESRD trait in Blacks.
  
  
  CONCLUSIONS
  The GFR decline/progression rate in hypertensive renal disease is controlled in part by genetic variation within the adrenergic pathway.
authors.affiliation: Renal Division, Peking University First Hospital, Beijing, China.
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Chen
authors.forename: Michael S
authors.initials: MS
authors.lastname: Lipkowitz
authors.forename: Rany M
authors.initials: RM
authors.lastname: Salem
authors.forename: Maple M
authors.initials: MM
authors.lastname: Fung
authors.forename: Vibha
authors.initials: V
authors.lastname: Bhatnagar
authors.forename: Manjula
authors.initials: M
authors.lastname: Mahata
authors.forename: Caroline M
authors.initials: CM
authors.lastname: Nievergelt
authors.forename: Fangwen
authors.initials: F
authors.lastname: Rao
authors.forename: Sushil K
authors.initials: SK
authors.lastname: Mahata
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Schork
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Hicks
authors.forename: Donald W
authors.initials: DW
authors.lastname: Bowden
authors.forename: Barry I
authors.initials: BI
authors.lastname: Freedman
authors.forename: Victoria H
authors.initials: VH
authors.lastname: Brophy
authors.forename: Daniel T
authors.initials: DT
authors.lastname: O'Connor
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D018450:Disease Progression; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000235:genetics; D006801:Humans; D006977:Hypertension, Renal / Q000188:drug therapy / Q000208:ethnology / Q000235:genetics; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D009400:Nephrosclerosis / Q000188:drug therapy / Q000208:ethnology / Q000235:genetics; D016032:Randomized Controlled Trials as Topic; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy / Q000208:ethnology / Q000235:genetics; D055815:Young Adult
chemical_list: D000959:Antihypertensive Agents; D018343:Receptors, Adrenergic, beta-2