单纯肥胖者早期动脉粥样硬化与体脂含量及β3肾上腺素能受体基因Trp64Arg突变

Early atherosclerosis and body fat content and β3-adrenergic gene Trp64Arg mutation in simple obesity subjects

目的:探讨β3-肾上腺素能受体(β3-adrenergicreceptor,β3-AR)基因Trp64Arg突变与单纯肥胖者早期动脉粥样硬化(atherosclerosis,AS)的关系。方法:无心血管疾病和代谢性疾病的单纯超重/肥胖者295例,按照腰臀比分成周围性肥胖和中心性肥胖组,172例正常体质量的健康人作为对照组。检测各组β3-AR基因Trp64Arg突变频率和血管内皮依赖性舒张功能(endothelium-dependentdilation,EDD),并测定空腹血糖、胰岛素、内皮素和一氧化氮。按稳态模式评估法公式计算胰岛素敏感性。结果:①周围性肥胖组和中心性肥胖组的EDD均较正常体质量组显著降低犤分别为(9.61±3.45)%,(7.36±3.65)%,(11.97±2.56)%,t=1.82,P<0.05,t=2.76,P<0.01犦,中心性肥胖组的EDD降低更明显(t=1.74,P<0.05)。中心性肥胖组一氧化氮水平较正常体质量组和周围性肥胖组显著下降犤分别为(65.03±19.11),(74.21±20.81),(71.92±17.03)μmol/L,t=2.03,2.15,P<0.05犦。②正常体质量组,周围性肥胖组和中心性肥胖组Trp64Arg突变频率分别为18.89%,17.17%和25.26%,后者与周围性肥胖组和正常体质量组比较差异虽无显著性意义(χ2=2.461,2.140,P>0.05),但有明显升高趋势。③周围性肥胖组EDD降低在β3-AR基因突变与无突变者之间差异无显著性意义。

AIM:To explore the relationship between β 3 adrenergic receptor (β 3 AR) gene Trp64Arg mutation and early atherosclerosis (AS) in simple obesity subjects. METHODS:A total of 295 overweight and simple obese subjects with no cardiovascular and metabolic disease were divided into peripheral obesity group and central obesity group according to the waist to hip ratio(WHR). Another 172 health subjects with normal weight were chosen as the control group.Mutation frequency of the Trp64Arg mutation in the β 3 AR gene and flow mediated endothelium dependent dilation(EDD) and other clinical parameters,such as fasting blood glucose(FBG),fasting insulin(FINS),plasma endothelin(ET) and nitric oxide(NO) were measured in all subjects. Homeostasis model assessment(HOMA) was applied to calculate insulin sensitivity. RESULTS:① EDD was reduced significantly in both peripheral and central obesity groups compared with control group[(9.61± 3.45)% ,( 7.36± 3.65) % ,(11.97± 2.56)% ,t=1.82,P< 0.05,t =2.76,P< 0.01)],which was more significant in central obesity subjects(t =1.74,P< 0.05). The level of NO in central obesity groups was also lower than those in the other two groups[(65.03± 19.11) μ mol/L ,( 74.21± 20.81) μ mol/L and ( 71.92± 17.03) μ mol/L,t=2.03,2.15,P< 0.05)].② The mutation frequency of the Trp64Arg was similar among peripheral obesity group( 17.17% ) ,central obesity group( 25.26% ) and control groups(18.89% ),which showed an upward tendency but no statistical significance between central obesity group and the other two groups(χ 2=2.461, 2.140, P >0.05).③ There were no significant differences of the decrease of EDD between mutation and non mutation subjects in peripheral obesity group. EDD in subjects with mutation[(6.32± 3.54)% ] decreased more significantly than those with no mutation[(8.56± 3.69)% ](t=2.27,P< 0.05).④ FINS and insulin sensitivity in both obesity groups were higher than those in the control group, while there were no significant differences between β 3 AR mutation and non mutation subjects in each group. CONCLUSION:Early AS is correlative to content and distribution of body fat and insulin resistance,the β 3 AR gene Trp64Arg mutation is also an important factor participating in AS.