应用基因芯片技术检测中国成年肥胖者外周血的基因表达谱

Peripheral blood gene expression profile of Chinese adult obesities by gene chip technique

背景:肥胖是全世界最常见、花费最大的代谢性疾病,基因及环境因素已经成为肥胖研究的焦点因素之一,基因芯片技术已被用于脂肪组织的研究。目的:采用基因芯片技术,首次测定中国成年肥胖者的外周血基因表达谱。设计:对照观察。单位:北京中医药大学。对象:由北京中医药大学基础医学院于2003-08/2004-05组织,按国际体质量标准在北京市工人疗养院筛选5例肥胖者和3例体质量正常者。5例肥胖者中男4例,女1例,年龄(21±1)岁;3例体质量正常者中男2例,女1例,年龄(26±5)岁。所有受试人员对实验方案均知情同意,且得到医院伦理道德委员会批准。方法:取上述受试者的外周血,提取总RNA并进行扩增和标记,用Test3芯片检测受试样品的质量,用U133A芯片进行基因表达谱观察,并将所得数据进行统计学分析,从基因BANK中查出具有显著差异的序列所标志的基因。主要观察指标:基因表达信号值。结果:与体质量正常者相比,肥胖者外周血基因表达谱显著上调的基因有66个,显著下调的基因有28个;其中上调超过2倍的有11个,下调超过2倍的有6个。肥胖者表达上调超过4倍的基因为HLA-DQA1,CRAT,MAPK8I3和DKFZP434N1923,其中表达上调超过20倍的基因为HLA-DQA1。结论:首次发现肥胖成人的外周血相关基因表达与体质量正常者有明显差异,肥胖与MHCⅡ类抗原HLA-DQA1,HLA-DQB1表达密切相关。

BACKGROUND： Obesity has become the most common and costly metabolic problem in the world, and the genetic and environmental effects on the generation of obesity have become one of the focus factors in obesity research. Gene-chips have been reported as a useful tool in human adipose tissue research. OBJECTIVE： To determine the peripheral blood gene expression profile of Chinese adult obesities by gene chip technique for the first time. DESIGN： Randomized controlled observation. SETTING： Beijing University of Traditional Chinese Medicine. PARTICIPANTS： The experiment was performed at the Basic Medical College of Beijing University of Traditional Chinese Medicine between August 2003 and May 2004. Five obese patients, 4 males and 1 female, aged （21.4±0.9） years and three non-obese persons, 2 males and 1 female, aged （26.0±5.3） years were selected by the international body mass index （BMI） standard. The written informed consent was obtained from all subjects, and the research was approved by the medical ethical committee of Beijing University of Traditional Chinese Medicine. METHODS： Total RNA was extracted from peripheral blood, amplified and labeled. The quality and quantity of the processed samples were checked by Test3 array. The gene expression profiles were monitored by U133A set. The data was analyzed statistically, and the gene symbols with significant difference were searched in Gene BANK database. MAIN OUTCOME MEASURES： Gene expression signal. RESULTS： Compared with non-obese adults, 66 genes showed up-regnlated expression and 28 genes showed down-regnlated, of which 11 genes were up-regnlated above twofold, and 6 genes were down-regulated above twofold. The results demonstrated that HLA-DQA1 （human leucocytic antigens）, CRAT, MAPK813 and DKF-ZP434N1923 genes were up-regnlated above 4 fold, and HLA-DQA1 gene was even up-regnlated above 20 fold. CONCLUSION： Significant differences in peripheral blood gene expression profiles in Chinese adult obesities are found for the first time. The results indicate that obesity is strongly associated with MHC class Ⅱ antigen HLA-DQA1, and HLA-DQB 1, etc.