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.
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.
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.
Our collective findings suggest that expression of PPARGC1A and lower mitochondrial number affect the metabolic phenotype in TS subjects.
Funding source: Academie de Recherche et D’Enseignement Superieur of Belgique
Award Identifier / Grant number: 2016-157E
We are extremely grateful to all women with Turner syndrome who took part in this study. We acknowledge the contribution of the Ecuadorian Foundation in Support of Turner Syndrome.
Research funding: This study was supported by the Academie de Recherche et D’Enseignement Superieur of Belgique (grant numbers 2016-157E).
Author contributions: The authors’ contribution to the paper is as follow FAN: study concepts and design, data analysis and interpretation, statistical analysis, obtaining funding, critical revision of the manuscript for important intellectual content and manuscript preparation; MS: molecular and data analysis; DB: biochemical studies and data analysis; YV: molecular and data analysis; MR-O: biochemical studies and data analysis. All authors read and approved the final manuscript.
Competing interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Informed consent: Informed consent was obtained from all individuals included in this study.
Ethical approval: The procedures employed were in keeping with the principles of the Institutional Committee on Ethics in Human Research and the Declaration of Helsinki of 1964 and subsequent modifications.
Data availability: The raw data supporting the conclusions of this manuscript will be made available upon request.
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