PPARGC1A promoter DNA-methylation level and glucose metabolism in Ecuadorian women with Turner syndrome

Abstract

Objectives: Reduced gene expression of PPARGC1A in subjects with insulin resistance (IR) has been reported. Insulin resistance occurs early on the course of Turner syndrome (TS). The main objective of this study was to evaluate the relationship between PPARGC1A promoter DNA methylation status in lymphocytes and insulin sensitivity and secretion in Ecuadorian females with TS.

Methods: We examined a cohort of 34 Ecuadorian patients with TS along with a sex-, age- and BMI-matched reference group. All subjects received a standard 75 g oral glucose tolerance test. Insulin resistance and secretion indices were calculated. The PPARGC1A methylated DNA/unmethylated DNA ratio and mitochondrial content (mtDNA/nDNA ratio) were further determined.

Results: Notably, the PPARGC1A DNA methylation level was significantly higher in TS subjects than the reference group and correlated with IR indices. Conversely, mitochondrial content was significantly lower in the study group than healthy controls and negatively correlated with the PPARGC1A methylated DNA/unmethylated DNA ratio in TS individuals. PPARGC1A promoter DNA methylation status contributed to 20% of the total variability in Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) independently of BMI or age in TS subjects.

Conclusions: Our collective findings suggest that expression of PPARGC1A and lower mitochondrial number affect the metabolic phenotype in TS subjects.

Keywords: DNA methylation; PPARGC1A; Turner syndrome; insulin resistance; pancreatic β-cell function.