Methylation of TFAM gene promoter in peripheral white blood cells is associated with insulin resistance in adolescents

• Published in: Molecular genetics and metabolism Vol. 100; no. 1; pp. 83 - 87
• Main Authors: Gemma, Carolina, Sookoian, Silvia, Dieuzeide, Guillermo, García, Silvia I., Gianotti, Tomas Fernández, González, Claudio D., Pirola, Carlos J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.05.2010
• Subjects: Adolescence; Adolescent; Adolescents; Base Sequence; DNA Methylation; DNA-Binding Proteins - genetics; Epigenetics; Female; Humans; Insulin resistance; Insulin Resistance - genetics; Leukocytes - metabolism; Male; Metabolic syndrome; Metabolic Syndrome - genetics; Mitochondrial Proteins - genetics; Molecular Sequence Data; Promoter Regions, Genetic; Sp1 Transcription Factor - metabolism; TFAM; Transcription Factors - genetics; DNA methylation; Epigenetics; Insulin resistance; TFAM; Adolescents; Metabolic syndrome
• ISSN: 1096-7192; 1096-7206
• DOI: 10.1016/j.ymgme.2010.02.004

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 (β: −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.