Oncotarget

Research Papers:

Differential DNA methylation patterns of polycystic ovarian syndrome in whole blood of Chinese women

Shuxia Li, Dongyi Zhu, Hongmei Duan, Anran Ren, Dorte Glintborg, Marianne Andersen, Vibe Skov, Mads Thomassen, Torben Kruse and Qihua Tan _

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Oncotarget. 2017; 8:20656-20666. https://doi.org/10.18632/oncotarget.9327

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Abstract

Shuxia Li1,*, Dongyi Zhu2,3,*, Hongmei Duan4, Anran Ren2,3, Dorte Glintborg5, Marianne Andersen5, Vibe Skov6, Mads Thomassen1, Torben Kruse1, Qihua Tan1,7

1Unit of Human Genetics, Department of Clinical Research, University of Southern Denmark, Odense, Denmark

2Center of Reproductive Medicine, Linyi People’s Hospital, Linyi, China

3Department of Obstetrics and Gynecology, Shandong Medical College, Linyi, China

4Department of Medicine, Kolding Hospital, Kolding, Denmark

5Department of Endocrinology, Odense University Hospital, Odense, Denmark

6Department of Hematology, Roskilde Hospital, Roskilde, Denmark

7Epidemiology, Biostatistics, and Biodemography, Department of Public Health, University of Southern Denmark, Odense, Denmark

*These authors contributed equally to this work

Correspondence to:

Qihua Tan, email: qtan@health.sdu.dk

Keywords: polycystic ovarian syndrome, DNA methylation, genome-wide association study, clinical heterogeneity

Received: January 26, 2016     Accepted: April 26, 2016     Published: May 12, 2016

ABSTRACT

As a universally common endocrinopathy in women of reproductive age, the polycystic ovarian syndrome is characterized by composite clinical phenotypes reflecting the contributions of reproductive impact of ovarian dysfunction and metabolic abnormalities with widely varying symptoms resulting from interference of the genome with the environment through integrative biological mechanisms including epigenetics. We have performed a genome-wide DNA methylation analysis on polycystic ovarian syndrome and identified a substantial number of genomic sites differentially methylated in the whole blood of PCOS patients and healthy controls (52 sites, false discovery rate < 0.05 and corresponding p value < 5.68e–06), highly consistently replicating biological pathways extensively implicated in immunity and immunity-related inflammatory disorders (false discovery rate < 0.05) that were reportedly regulated in the DNA methylome from ovarian tissue under PCOS condition. Most importantly, our genome-wide profiling focusing on PCOS patients revealed a large number of DNA methylation sites and their enriched functional pathways significantly associated with diverse clinical features (levels of prolactin, estradiol, progesterone and menstrual cycle) that could serve as novel molecular basis of the clinical heterogeneity observed in PCOS women.


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