Document Detail


Progression of chronic kidney disease: Adrenergic genetic influence on glomerular filtration rate decline in hypertensive nephrosclerosis.
MedLine Citation:
PMID:  20484896     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Yuqing Chen; Michael S Lipkowitz; Rany M Salem; Maple M Fung; Vibha Bhatnagar; Manjula Mahata; Caroline M Nievergelt; Fangwen Rao; Sushil K Mahata; Nicholas J Schork; Pamela J Hicks; Donald W Bowden; Barry I Freedman; Victoria H Brophy; Daniel T O'Connor;
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2010-05-19
Journal Detail:
Title:  American journal of nephrology     Volume:  32     ISSN:  1421-9670     ISO Abbreviation:  Am. J. Nephrol.     Publication Date:  2010  
Date Detail:
Created Date:  2010-07-19     Completed Date:  2010-10-25     Revised Date:  2012-10-09    
Medline Journal Info:
Nlm Unique ID:  8109361     Medline TA:  Am J Nephrol     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  23-30     Citation Subset:  IM    
Copyright Information:
Copyright 2010 S. Karger AG, Basel.
Affiliation:
Renal Division, Peking University First Hospital, Beijing, China.
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MeSH Terms
Descriptor/Qualifier:
Adult
African Americans / genetics*
Aged
Antihypertensive Agents / therapeutic use*
Disease Progression
Drug Resistance / genetics
Female
Glomerular Filtration Rate / drug effects,  genetics
Humans
Hypertension, Renal* / drug therapy,  ethnology,  genetics
Male
Middle Aged
Multicenter Studies as Topic
Nephrosclerosis* / drug therapy,  ethnology,  genetics
Randomized Controlled Trials as Topic
Receptors, Adrenergic, beta-2 / genetics*
Renal Insufficiency, Chronic* / drug therapy,  ethnology,  genetics
Young Adult
Grant Support
ID/Acronym/Agency:
M01 RR000827/RR/NCRR NIH HHS; M01 RR000827-346233/RR/NCRR NIH HHS; MD000220/MD/NIMHD NIH HHS; P01 HL058120/HL/NHLBI NIH HHS; P01 HL058120-10/HL/NHLBI NIH HHS; P60 MD000220-10/MD/NIMHD NIH HHS; RR00827/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Antihypertensive Agents; 0/Receptors, Adrenergic, beta-2
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