Department of Molecular Genetics and Biology of Complex Diseases, Institute of Medical Research, A. Lanari-IDIM, University of Buenos Aires, National Council of Scientific and Technological Research (CONICET), Ciudad Autónoma de Buenos Aires C1427ARO, Argentina.
Mol Genet Metab. 2010 May;100(1):83-7. doi: 10.1016/j.ymgme.2010.02.004. Epub 2010 Feb 12.
To explore whether DNA methylation of the mitochondrial transcription factor A (TFAM) promoter is associated with insulin resistance in a sample of adolescents with features of metabolic syndrome.
The data and blood samples were collected from 122 adolescents out of a cross-sectional study of 934 high-school students. The population was divided into two groups: noninsulin resistance (NIR) and insulin resistance (IR). After bisulfite treatment of genomic DNA from peripheral leukocytes, we used methylation-specific polymerase chain reaction (PCR) to assess DNA methylation of three putative methylation target sites (CpG) in the TFAM promoter.
The ratio of the promoter methylated DNA/unmethylated DNA was 0.012+/-0.0009 (1.2% of alleles), and inversely correlated with the biochemical features of insulin resistance (plasma fasting insulin R: -0.26, p<0.004 and homeostasis model assessment (HOMA) index R: -0.27, p<0.002), and obesity (R: -0.27, p<0.002). Multiple regression analysis showed that the log-transformed HOMA index correlated with the status of promoter methylation of TFAM, independently of body mass index (BMI) Z score (beta: -0.33+/-0.094, p=0.00094). Finally, the TFAM promoter methylated DNA/unmethylated DNA ratio was found to be significantly associated with insulin resistance as dichotomous variable (NIR n=45, 0.014+/-0.002 and IR n=77, 0.011+/-0.001, respectively, p<0.016).
Our findings suggest a potential role of promoter TFAM methylation in the pathogenesis of insulin resistance in adolescents.
在患有代谢综合征特征的青少年样本中，探索线粒体转录因子 A（TFAM）启动子的 DNA 甲基化是否与胰岛素抵抗有关。
从一项横断面研究的 934 名高中生中抽取了 122 名青少年的数据和血液样本。人群分为两组：非胰岛素抵抗（NIR）和胰岛素抵抗（IR）。外周白细胞基因组 DNA 经亚硫酸氢盐处理后，我们使用甲基化特异性聚合酶链反应（PCR）来评估 TFAM 启动子中三个假定甲基化靶位（CpG）的 DNA 甲基化。
启动子甲基化 DNA/未甲基化 DNA 的比值为 0.012+/-0.0009（等位基因的 1.2%），与胰岛素抵抗的生化特征呈负相关（血浆空腹胰岛素 R：-0.26，p<0.004 和稳态模型评估（HOMA）指数 R：-0.27，p<0.002），与肥胖呈负相关（R：-0.27，p<0.002）。多元回归分析表明，log 转换的 HOMA 指数与 TFAM 启动子甲基化状态相关，独立于体重指数（BMI）Z 评分（β：-0.33+/-0.094，p=0.00094）。最后，发现 TFAM 启动子甲基化 DNA/未甲基化 DNA 的比值与胰岛素抵抗作为二分类变量显著相关（NIR n=45，0.014+/-0.002 和 IR n=77，0.011+/-0.001，分别，p<0.016）。
我们的研究结果表明，TFAM 启动子甲基化在青少年胰岛素抵抗的发病机制中可能具有潜在作用。
