Epigenetic regulation of an adverse metabolic phenotype in polycystic ovary syndrome: the impact of the leukocyte methylation of PPARGC1A promoter

Abstract

Objective: To investigate PPARGC1A promoter methylation and mitochondria DNA (mtDNA) content in the leukocytes of women with polycystic ovary syndrome (PCOS) and analyze the relationship between these indices and metabolic risk for women with PCOS.

Design: Cross-sectional study.

Setting: University hospital.

Patient(s): A total of 175 women with PCOS and 127 healthy controls.

Intervention(s): None.

Main outcome measure(s): Women with and without PCOS classified using the typical metabolic risk criteria of the National Cholesterol Education Program's Adult Treatment Panel III report (ATPIII), methylation of PPARGC1A promoter tested by methylation-specific polymerase chain reaction, and mtDNA content confirmed by quantitative polymerase chain reaction (PCR).

Result(s): PPARGC1A promoter methylation was specifically increased, but mtDNA content was specifically decreased in women with PCOS compared with the control women after adjustment for body mass index. Moreover, in women with PCOS who have increased metabolic risk, the differences in PPARGC1A promoter methylation and mitochondrial content were aggravated.

Conclusion(s): In conclusion, PPARGC1A promoter methylation and mitochondrial content were found to be potential biomarkers for the prediction of metabolic risk in women with PCOS.

Keywords: ATPIII; BMI; lipid profile; metabolic risk; mitochondrial biogenesis.