β3肾上腺素能受体基因Trp64Arg突变与单纯肥胖者早期动脉粥样硬化的相关研究

ASSOCIATION OF β3-ADRENERGIC GENE Trp64Arg MUTATION WITH EARLY ARTERIOSCLEROSIS IN SIMPLE OBESITY SUBJECTS

目的探讨 β3 肾上腺素能受体 (β3 adrenergicreceptor,β3 AR)基因Trp6 4Arg突变与单纯肥胖者早期动脉粥样硬化形成的关系。方法 2 95例无心血管疾病和代谢性疾病的单纯超重 /肥胖者 ,按照腰臀比分为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。检测各组 β3 AR基因Trp6 4Arg突变频率和血管内皮依赖性舒张功能 (endothelium dependentdilation ,EDD) ,并测定空腹时血糖 (fastingbloodglucose,FBG)、胰岛素(fastinginsulin ,FINS)、内皮素 (endothelin ,ET)和一氧化氮 (nitricoxide,NO) ,按稳态模式评估法公式计算胰岛素敏感性 (hemeostasismodelassessmentforinsulinresistance ,HOMA IR)。结果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 (P <0 .0 5 ,P <0 .0 1) ,前 2组比较 ,中心性肥胖组EDD降低更明显 ,且NO水平也显著下降 (P均 <0 .0 5 ) ;周围性肥胖组 ,中心性肥胖组和正常体质量组Trp6 4Arg突变频率分别为 17.17% ,2 5 .2 6 %和 18.89% ,虽无显著性差异 ,但中心性肥胖组与其他 2组比较 ,有明显升高趋势 ;周围性肥胖组EDD降低在β3 AR基因突变与无突变者之间无显著性差异 ,而中心性肥胖组的EDD在基因突变者较无突变者降低更显著 (P <0 .0 5 )。

ObjectiveTo explore the relationship between β3-adrenergic receptor (β3-AR) gene Trp64Arg mutation with early atherosclerosis in the simple obesity subjects. Methods295 overweight and obesity subjects were divided into two groups including peripheral obesity and central obesity according to the waist-hip ratio (WHR). 172 healthy subjects with normal body mass served as a control group. Geno-typing of the Trp64Arg mutation in the β3-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 HOMA-IR as an index of insulin resistance. ResultsEDD was reduced in both peripheral and central obesity groups compared with control group. The change was more obvious in central obesity subjects,whose level of NO also was lower than peripheral obesity and control subjects. The allelic frequency of the Trp64Arg mutation was similar among peripheral obesity,central obesity and control groups ( 17.17 , 25.26 and 18.89 ,respectively),which showed an upward tendency,but no significant differences were found in central obesity subjects compared with peripheral obesity and control subjects. EDD was significantly reduced in subjects with Trp64Arg and Arg64Arg genotypes compared with Trp64Trp genotype in central obesity group,but no significant difference were found between mutation and non-mutation subjects in peripheral obesity group. ConclusionEarly atherosclerosis in simple obesity subjects is correlative to total body fat and body fat distribution,the β3-AR gene Trp64Arg mutation also is an important factor participating in atherosclerosis.