Abstract 3932: High Plasma Norepinephrine Level Determined by β2 adrenoceptor Polymorphisms Predicts the Future Renal Injury in Nonobese, Normotensive Individuals
Background: Renal injury is one of the common organ damage caused by hypertension. In the present study, we examined the relationships between the β2-adrenoceptor polymorphisms, alterations of renal function (blood urea nitrogen (BUN) and creatinine) and plasma norepi-nephrine (NE) levels in a longitudinal design over 5 years.
Methods: In 219 nonobese, normotensive men with entry normal renal function, we measured the β2 (Arg16Gly, Gln27Glu)-adrenoceptor polymorphisms, serum BUN, creatinine, plasma NE, the homeostasis model assessment of insulin-resistance (HOMA), BMI, total body fat mass and blood pressure (BP) annually over 5 years. The subjects were stable in body weight over 5 years and non-diabetic.
Results: High plasma NE was defined as a plasma NE level of ≥mean±1SD of 1.37 pmol/mL in the participants at entry. There were 37 subjects who had entry high plasma NE and 182 subjects who had entry normal plasma NE (<mean±1SD). Plasma NE level at entry was significantly higher in subjects with high plasma NE compared to those with normal plasma NE, but BUN, creatinine, HOMA, BMI, total body fat-mass and BP levels at entry were similar. Changes in serum BUN, creatine, plasma NE, HOMA, fat-mass, BMI and BP levels over a 5-year period were significantly greater in subjects with high plasma NE. Subjects with high plasma NE had significantly higher frequencies of the Gly16 allele of β2-adrenoceptor polymorphisms compared to those with normal plasma NE (χ2=58.32, P<0.001). Subjects carrying the Gly16 allele had higher levels of plasma NE, HOMA and total body fat-mass at entry, and greater increases in BUN, creatinine, plasma NE and fat-mass over 5 years. Changes in BUN over 5 years were significantly determined by plasma NE at entry (P=0.008), but not mean BP, BMI, total body fat-mass, HOMA-IR, leptin, BUN or creatinine (F=2.75, P=0.033, R2=0.271). Changes in serum creatinine was determined by plasma NE (P=0.018), leptin (P=0.049), mean BP (P=0.023), BMI (P=0.041) and total body fat-mass (P=0.033) at entry (F=2.39, P=0.045, R2=0.351).
Conclusions: High plasma NE levels at entry in part determined by the Gly16 of the β2-adrenoceptor polymorphisms predict elevations in BUN and creatinine over a 5-years period accompanied by greater increases in plasma NE and HOMA.