391 BETA2-ADRENOCEPTOR POLYMORPHISMS (ARG16GLY) IS RELATED TO RESISTANCE TO WEIGHT LOSS INDUCED IMPROVEMENTS OF CARDIAC- AND RENAL COMPLICATIONS

Abstract

Background: Obesity is an independent risk factor for cardiovascular and renal complications. We previously reported that the Arg16Gly, β2-adrenoceptor (ADRB2) polymorphism, accompanying high plasma norepinephrine (NE) could predict future weight gain, BP elevation and renal injury. The 1st line of treatment for obesity is weight loss (WL). In this study, we evaluated the relationships between ADRB2 polymorphisms (Arg16Gly), prevalence of LVH and renal function (creatinine clearance) over 2 years with WL program. Methods: Obese Japanese men (n = 154) were measured BMI, BP, plasma NE, leptin, creatinine, creatinine clearance (CCr), LVH determined by ECG and ADRB2 polymorphisms (Arg16Gly, Gln27Glu) before and after WL program (low caloric diet + exercise) over 2 years. Significant WL was defined >10% WL of entry BMI. Results: Significant WL was noted in 97 (63%) subjects and the frequencies of Gly16 were 39% for WL group vs. 54% for non-WL group (P < 0.05). At entry, subjects with Gly16 allele had higher levels of plasma NE, leptin, creatinine, higher prevalence of LVH, and lower CCr compared to those without Gly16 allele. WL group had lower fat-mass, NE, leptin and creatinine and LVH prevalence and higher CCr at entry compare dto non-WL group. WL group had greater changes in BMI, fat-mass, creatinine and CCr, and greater % reductions in NE and leptin over a 2-year period. Changes in fat-mass correlated with changes in creatinine, CCr, NE and BP over 2 years. Changes in plasma NE correlated with changes in CCr. In multiple regression analysis, plasma NE, fat-mass and BP levels were determinants for prevalence of LVH at entry and 2-year period. Conclusions: ADRB2 polymorphisms (Arg16Gly) accompanying high plasma NE is related to the prevalence of LVH and improving CCr with WL. Arg16Gly associated with high plasma NE may play an important role in cardio- and renal-complications in obesity.