Methylation in CpG sites of the PPARGC1A gene (encoding PGC1-α) has been associated
with adiposity, insulin secretion/sensitivity indexes and type 2 diabetes. We assessed the association
between the methylation profile of the PPARGC1A gene promoter gene in leukocytes with insulin
secretion/sensitivity indexes in normoglycemic women. A standard oral glucose tolerance test (OGTT)
and an abbreviated version of the intravenous glucose tolerance test (IVGTT) were carried out in
n = 57 Chilean nondiabetic women with measurements of plasma glucose, insulin, and C-peptide.
Bisulfite-treated DNA from leukocytes was evaluated for methylation levels in six CpG sites of the
proximal promoter of the PPARGC1A gene by pyrosequencing (positions -816, -783, -652, -617, -521
and -515). A strong correlation between the DNA methylation percentage of different CpG sites of the
PPARGC1A promoter in leukocytes was found, suggesting an integrated epigenetic control of this
region. We found a positive association between the methylation levels of the CpG site -783 with the
insulin sensitivity Matsuda composite index (rho = 0.31; p = 0.02) derived from the OGTT. The CpG
hypomethylation in the promoter position -783 of the PPARGC1A gene in leukocytes may represent a
biomarker of reduced insulin sensitivity after the ingestion of glucose
