北京大学医学部机构知识库
Advanced  
IR@PKUHSC  > 北京大学第一临床医学院  > 肾脏内科  > 期刊论文
学科主题: 临床医学
题名:
Common Charge-Shift Mutation Glu65Lys in K+ Channel beta(1)-Subunit KCNMB1: Pleiotropic Consequences for Glomerular Filtration Rate and Progressive Renal Disease
作者: Chen, Yuqing1,2; Salem, Rany M.2; Rao, Fangwen2; Fung, Maple M.2,5; Bhatnagar, Vibha2,5; Pandey, Braj2,5; Mahata, Manjula2; Waalen, Jill6; Nievergelt, Caroline M.2,5; Lipkowitz, Michael S.7; Hamilton, Bruce A.2,4; Mahata, Sushil K.2,5; O′ Connor, Daniel T.2,3,4,5
关键词: Glomerular filtration rate ; KCNMB1 ; Hypertensive nephrosclerosis ; African-American Study of Kidney Disease and Hypertension
刊名: AMERICAN JOURNAL OF NEPHROLOGY
发表日期: 2010
DOI: 10.1159/000320131
卷: 32, 期:5, 页:414-424
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Urology & Nephrology
研究领域[WOS]: Urology & Nephrology
关键词[WOS]: KIDNEY-DISEASE ; BLOOD-PRESSURE ; AFRICAN-AMERICAN ; MESANGIAL CELLS ; CREATININE CLEARANCE ; BETA-1 SUBUNIT ; SMOOTH-MUSCLE ; HYPERTENSION ; POPULATION ; LINKAGE
英文摘要:

Background: Glomerular filtration rate (GFR) is a heritable trait, and hyperfiltration (GFR increment in remnant nephrons) may accelerate renal functional decline in chronic kidney disease (CKD). Mesangial and vascular smooth myocytes control GFR by contraction, dependent on voltage-gated Ca2+ influx, which is controlled by the regulatory beta(1)-subunit (KCNMB1) of large-conductance heteromeric K+ (′BK′) channels. KCNMB1 gain-of-function variant Glu65Lys results in generalized vasorelaxation and thus protection against systemic hypertension. Here we asked whether the Glu65Lys variant influences GFR, in the basal state or during progressive renal decline. Methods: We explored Glu65Lys effects on GFR in three populations spanning two ethnicities and two diseases (hypertension and nephrosclerosis). GFR was either estimated (eGFR from serum creatinine) or directly measured (iothalamate clearance). Results: The 65Lys variant was relatively common, occurring on similar to 5-10% of chromosomes in different biogeographic ancestry groups, and 65Lys carriers exhibited higher eGFR in two primary care populations: extreme BP values in Kaiser clinics (p = 0.029, accounting for similar to 0.2% of trait variance), or treated hypertensives in VA clinics (p = 0.017, accounting for similar to 0.9% of trait variance). In blacks with progressive renal disease (NIDDK AASK), 65Lys carriers displayed a steeper slope in GFR chronic decline (p = 0.030, accounting for similar to 0.4% of trait variance), and Glu65Lys genotype also predicted time of onset of renal failure (log rank p = 0.019). Conclusions: Common KCNMB1 gain-of-function variant Glu65Lys influences GFR, and 65Lys carriers exhibit not only elevated baseline GFR, but also more rapid GFR decline (and consequent development of renal failure) in CKD. The results suggest that profiling patients at Glu65Lys can assist in gauging renal prognosis as well as selection of rational therapy in hypertension with progressive renal disease. Copyright (C) 2010 S. Karger AG, Basel

语种: 英语
所属项目编号: NIH RR00827 ; NIH MD000220 ; NIH DK079337
项目资助者: UCSD General Clinical Research Center ; UCSD Comprehensive Research Center in Health Disparities (CRCHD) ; UAB/UCSD O&prime ; Brien Kidney Disease Research Center ; International Society of Nephrology ; National Institutes of Health, Department of Veterans Affairs, International Society of Nephrology
WOS记录号: WOS:000284282900004
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/60963
Appears in Collections:北京大学第一临床医学院_肾脏内科_期刊论文

Files in This Item:

There are no files associated with this item.


作者单位: 1.Peking Univ, Div Renal, Hosp 1, Dept Med, Beijing 100034, Peoples R China
2.Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA
3.Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA
4.Univ Calif San Diego, Inst Genom Med, La Jolla, CA 92093 USA
5.VA San Diego Healthcare Syst, La Jolla, CA USA
6.Scripps Res Inst, La Jolla, CA 92037 USA
7.Mt Sinai Sch Med, New York, NY USA

Recommended Citation:
Chen, Yuqing,Salem, Rany M.,Rao, Fangwen,et al. Common Charge-Shift Mutation Glu65Lys in K+ Channel beta(1)-Subunit KCNMB1: Pleiotropic Consequences for Glomerular Filtration Rate and Progressive Renal Disease[J]. AMERICAN JOURNAL OF NEPHROLOGY,2010,32(5):414-424.
Service
Recommend this item
Sava as my favorate item
Show this item's statistics
Export Endnote File
Google Scholar
Similar articles in Google Scholar
[Chen, Yuqing]'s Articles
[Salem, Rany M.]'s Articles
[Rao, Fangwen]'s Articles
CSDL cross search
Similar articles in CSDL Cross Search
[Chen, Yuqing]‘s Articles
[Salem, Rany M.]‘s Articles
[Rao, Fangwen]‘s Articles
Related Copyright Policies
Null
Social Bookmarking
Add to CiteULike Add to Connotea Add to Del.icio.us Add to Digg Add to Reddit

Items in IR are protected by copyright, with all rights reserved, unless otherwise indicated.

 

 

Valid XHTML 1.0!
Copyright © 2007-2017  北京大学医学部 - Feedback
Powered by CSpace