Abstract P018: Weight Loss Related to Gly16 of Arg16Gly Polymorphism Contribute to the Improvement of Renal Function and Left Ventricular Hypertrophy in Obesity
Background:Obesity is an independent risk factor for cardiovascular and renal complications, and sympathetic activation play an important role of the onset or development of cardiac- and renal-complications. The Gly16 allele of Arg16Gly, β2-adrenoceptor polymorphism, accompanying high plasma norepinephrine (NE) is reported as a strong linkage with the pathogenesis of obesity, hypertension and renal function through sympathetic activity. In this study, we evaluated the effects of WL on cardiac- (LVH) and renal (creatinine clearance; CCr) - functions in obese hypertensive patient. In addition, the relation of Arg16Gly polymorphism with cardiac- and renal function were examined.
Methods: Overweighto Obese, hypertensive men (n=154) on no medications were measured BMI, blood pressures (BP), plasma NE, HOMA-IR, CCr, LVH determined by ECG (SV1+RV5 or 6>35) and Arg16Gly polymorphism before and after WL program (low caloric diet + exercise) over 2 years. Significant WL was defined as10% or more WL of entry BMI.
Results: Significant WL at 2 yrs 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). Subjects with Gly16 were resistant in significant WL over 2 years or rebound weight gain. Subjects with significant WL and those without Gly16 allele had significantly lower fat-mass, BPs, NE, HOMA-IR, LVH prevalence and LVH index (SV1+RV5 or 6), and higher CCr at entry compared to subjects without WL or those with Gly16 allele. The significant WL group and those without Gly16 allele had significantly greater decreases in BMI, fat-mass, %NE, HOMA, LVH prevalence, LVH index and increase in CCr compared to the group without significant WL or with Gly16 allele. Changes in fat-mass correlated with changes in CCr, plasma NE and BP over 2 yrs. Changes in plasma NE correlated negatively with changes in CCr. Changes in LVH index (SV1+RV5 or 6) correlated positively with changes in BMI. Of importance, all subjects who were on WL program, regardless of success on significant WL, had improvements on CCr or LVH index at 2-yrs.
Conclusions: WL could improve cardiac (observed in LVH)- and renal (observed in CCr) functions in obese, hypertensive patients. High plasma NE determined by Arg16Gly polymorphisms may play an important role in cardio- and renal-complications in obesity. WL program, itself, may improve cardiac- and renal complications through suppression on sympathetic activation and normalization on insulin resistance.
- © 2013 by American Heart Association, Inc.