PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: Our findings suggest a potential role of promoter TFAM methylation in the pathogenesis of insulin resistance in adolescents. (c) 2010 Elsevier Inc. All rights reserved.
PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: Our findings suggest a potential role of promoter TFAM methylation in the pathogenesis of insulin resistance in adolescents. (c) 2010 Elsevier Inc. All rights reserved.
Authors: Rodrigo San-Cristobal; Santiago Navas-Carretero; Fermín I Milagro; J Ignacio Riezu-Boj; Elizabeth Guruceaga; Carlos Celis-Morales; Katherine M Livingstone; Lorraine Brennan; Julie A Lovegrove; Hannelore Daniel; Wim H Saris; Iwonna Traczyk; Yannis Manios; Eileen R Gibney; Michael J Gibney; John C Mathers; J Alfredo Martinez Journal: J Physiol Biochem Date: 2017-03-28 Impact factor: 4.158
Authors: Alexis C Frazier-Wood; Stella Aslibekyan; Devin M Absher; Paul N Hopkins; Jin Sha; Michael Y Tsai; Hemant K Tiwari; Lindsay L Waite; Degui Zhi; Donna K Arnett Journal: J Lipid Res Date: 2014-04-07 Impact factor: 5.922