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


CONCLUSIONS
Our findings suggest a potential role of promoter TFAM methylation in the pathogenesis of insulin resistance in adolescents.
Gemma
Carolina
C
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.
Sookoian
Silvia
S
Dieuzeide
Guillermo
G
García
Silvia I
SI
Gianotti
Tomas Fernández
TF
González
Claudio D
CD
Pirola
Carlos J
CJ
D000293:Adolescent; D001483:Base Sequence; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics*; D024101:Mitochondrial Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D016329:Sp1 Transcription Factor / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics*
D004268:DNA-Binding Proteins; D024101:Mitochondrial Proteins; D016329:Sp1 Transcription Factor; C499631:TFAM protein, human; D014157:Transcription Factors