杉本 研
   Department     ,
   Position  
Article types 原著
Language English
Peer review Peer reviewed
Title High plasma norepinephrine levels associated with beta2-adrenoceptor polymorphisms predict future renal damage in nonobese normotensive individuals.
Journal Formal name:Hypertension research : official journal of the Japanese Society of Hypertension
Abbreviation:Hypertens Res
ISSN code:09169636/09169636
Domestic / ForeginForegin
Volume, Issue, Page 30(6),503-511頁
Author and coauthor Masuo Kazuko, Katsuya Tomohiro, Sugimoto Ken, Kawaguchi Hideki, Rakugi Hiromi, Ogihara Toshio, Tuck Michael L
Publication date 2007/06
Summary Renal injury is common in obesity and hypertension. In the present study, we examined relationships between renal function alterations, plasma norepinephrine (NE), and beta2-adrenoceptor polymorphisms in a longitudinal design over 5 years. In 219 nonobese, normotensive men with entry-normal renal function, we measured serum blood urea nitrogen (BUN), creatinine, creatinine clearance, plasma NE, homeostasis model assessment of insulin resistance (HOMA-IR), body mass index (BMI), total body fat mass, and blood pressure (BP) annually for 5 years. beta2 (Arg16Gly, Gln27Glu)-adrenoceptor polymorphisms were determined. The subjects were stable in body weight and BP (<10%) for 5 years. High plasma NE was defined as > or =mean+1 SD at entry. Thirty-seven subjects had entry-high plasma NE and 182 were entry-normal. Entry-high plasma NE subjects had significantly greater total body fat mass and plasma NE and significantly lower creatinine clearance at entry and throughout the study. Increases in BMI, fat mass, BP, plasma NE, BUN, and creatinine, as well as the reduction in creatinine clearance in the 5 years, were significantly greater in entry-high NE subjects. These subjects had significantly higher frequencies of the Gly16 allele of beta2-adrenoceptor polymorphisms. Throughout the study, subjects carrying the Gly16 allele had higher plasma NE, HOMA-IR, and fat mass, and significantly greater reductions in creatinine clearance. Plasma NE at entry was a determinant variable for changes in BUN, creatinine, and creatinine clearance over the 5-year period in multiple regression analysis. In conclusion, high plasma NE at entry, associated with the Gly16 allele of the beta2-adrenoceptor polymorphisms, predict renal function deterioration (seen in elevations of BUN and creatinine and reduction of creatinine clearance) over a 5-year period accompanying further heightened sympathetic nerve activity and deterioration of insulin resistance.
DOI 10.1291/hypres.30.503
PMID 17664853