PCOS is characterised by a specific epigenetic signature in peripheral blood mononuclear cells: A pilot study — ASN Events
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  3. PCOS is characterised by a specific epigenetic signature in peripheral blood mononuclear cells: A pilot study

PCOS is characterised by a specific epigenetic signature in peripheral blood mononuclear cells: A pilot study (#138)

Danielle S Hiam 1 , David Simar 2 , Melanie Gibson-Helm 3 , Helena J Teede 3 , Nigel K Stepto 1
  1. Institute of Sport, Exercise & Active Living, Victoria University, Melbourne, Victoria, Australia
  2. Inflammation and Infection Research, School of Medical Sciences , University of New South Wales, Sydney, NSW, Australia
  3. Monash Centre for Health Research and Implementation (MCHRI), School of Public Health & Preventive Medicine, Monash University, Melbourne, Victoria , Australia

Polycystic Ovary Syndrome (PCOS) affects 9-18% of Australian women placing them at a 4-8 fold greater risk of developing Type 2 Diabetes. The cause of the syndrome is unclear but has been associated with an intrinsic insulin resistance and chronic low-grade inflammation. These mechanisms likely involve the interactions between genetics and lifestyle, a research field known as epigenetics. Epigenetic modifications, such as DNA methylation, alter chromatin structure and gene expression and have been linked to insulin-resistant diseases such as Type 2 Diabetes and PCOS. Despite this, it is unknown whether this occurs in immune cells, which may link inflammation and insulin resistance.  Therefore we aimed to investigate whether women with PCOS have altered DNA methylation profiles in their Peripheral Blood Mononuclear Cells (PBMC) which may drive inflammation and contribute to the intrinsic insulin resistance in PCOS. Women with PCOS were diagnosed by the Rotterdam criteria. Blood samples were taken from women with and without PCOS. An oral glucose tolerance test and dual-energy X-ray absorptiometry were performed. PBMCs were isolated from whole blood and analysed by flow cytometry for cell-specific global DNA methylation. Women with PCOS were similar in age, BMI and body fat percentage to controls. They were less glucose tolerant as assessed by area under the glucose curve (mean±SD; 810±180 vs. 671±73; P=0.008) and had a higher postprandial glucose response compared to controls (6.1±1.8 vs. 5.0±0.5 mmol.L-1; P=0.039; PCOS n=15 and controls n=16). Preliminary findings (PCOS n=8 and controls n=6) show significant cell-specific hypo-methylation in PCOS vs. Controls of lymphocytes (P=0.049) and monocytes (P=0.01). This data suggests women with PCOS have an altered epigenetic signature in lymphocytes and monocytes that could be linked to the chronic low-grade inflammation and insulin resistance that is involved in the aetiology of PCOS.

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