Mutational analysis of the UCP2 core promoter and relationships of variants with obesity
Mutational analysis of the UCP2 core promoter and relationships of variants with obesity
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DOI：
10.1038/oby.2003.191
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发表时间：
2003-11-01
期刊：
影响因子：
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通讯作者：
Pedersen, O
中科院分区：
文献类型：
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作者：
Dalgaard, LT;Andersen, G;Pedersen, O
目的：为了确定在人类解偶联蛋白2基因（UCP 2）启动子的多态性，并调查这些是否与肥胖或weight gain.Research方法和程序：人类UCP 2启动子的特点是报告基因分析来自骨骼肌，白色脂肪组织，和胚胎组织的细胞系。我们分析了60名肥胖受试者的核心启动子多态性。一个流行的多态性，-866 G/A变异，被调查与肥胖的749名男性肥胖作为年轻的成年人和816名男性相同的年龄代表的背景人口。基因型-表型相互作用的研究中进行了其他两个人口为基础的样本：一组中年至老年丹麦科目（平均年龄，53岁;范围，30至88岁）和一组60岁的丹麦subjects.Results：该区域高达-1202 bp相对于UCP 2转录起始位点引起了最高的启动子活性。在该区域中鉴定出8个突变，包括-866 G/A、-850 G/A、-337 G/C、-41 G/T、-28插入T、-5插入T、-28插入T（cactgcgaagccc）、+45 C/T和+53 G/C，但这些都与BMI、体脂含量、体重增加或空腹血糖和血清胰岛素水平的一致性改变无关。在丹麦受试者中，UCP 2启动子的变异（包括单一常见变异（-866 A/G））与肥胖或肥胖相关的中间表型无关。
Objective: To identify polymorphisms in the human uncoupling protein 2 gene (UCP2) promoter and to investigate whether these were associated with obesity or weight gain.Research Methods and Procedures: The human UCP2 promoter was characterized by reporter gene analysis in cell lines derived from skeletal muscle, white adipose tissue, and embryonic tissue. We analyzed the core promoter for polymorphisms in 60 obese subjects. A prevalent polymorphism, the -866 G/A variant, was investigated for association with obesity in 749 men obese as young adults and 816 men of the same age representing the background population. Genotype-phenotype interaction studies were performed in two other population-based samples: one group of middle-aged-to-elderly Danish subjects (mean age, 53 years; range, 30 to 88 years) and one group of 60-year-old Danish subjects.Results: The region up to -1202 bp relative to the UCP2 transcription initiation site gave rise to the highest promoter activity. Eight mutations in this region were identified comprising -866 G/A, -850 G/A, -337 G/C, -41 G/T, -28 insertion T, -5 insertion (cactgcgaagccc), +45 C/T, and +53 G/C, but none of these was associated with consistent alterations in BMI, body fat content, weight gain, or fasting levels of plasma glucose and serum insulin.Discussion: Variation of the UCP2 promoter including the single common variant (-866 A/G) is not associated with obesity or obesity-related intermediary phenotypes in Danish subjects.