Endocrine Abstracts (2012) 28 P185

Association between rs1801260 of the circadian gene CLOCK and lipid and glucose metabolism in women with Polycystic Ovary Syndrome

Ida Pernicova1, Baris Akinci2, Madhu Prasai1, Paul Baxter3 & Eleanor Scott1

1Division of Cardiovascular and Diabetes Research, Leeds Institute of Genetics Health and Therapeutics, LIGHT Laboratories, University of Leeds, Leeds, United Kingdom; 2Division of Endocrinology, Dokuz Eylul University, Izmir, Turkey; 3Centre for Epidemiology and Biostatistics, University of Leeds, Leeds, United Kingdom; 4Division of Endocrinology, William Harvey Institute, London, United Kingdom.

Introduction: The circadian clock controls numerous aspects of mammalian physiology across the 24 hour day, including lipid and glucose metabolism. Disruption of the core circadian gene CLOCK is associated with the development of obesity, diabetes and the metabolic syndrome in mice. Women with Polycystic Ovary Syndrome (PCOS) are at increased risk of developing diabetes, dyslipidemia and the metabolic syndrome. The aim of the present study was to investigate the relationship of CLOCK SNP rs1801260 (3111T/C) to plasma glucose and lipids in premenopausal women with PCOS.

Methods: 182 premenopausal women (mean age 33 years), comprising 92 with PCOS (defined by the European Society of Human Reproduction and Embryology) and 90 healthy controls, were examined. Rs1801260 was genotyped from DNA extracted from leucocytes. Fasting plasma lipids (HDL cholesterol, triglycerides) and glucose were measured together with 120 min glucose in response to 75 g oral glucose tolerance test.

Results: There was no difference in genotype frequency between the PCOS subjects and healthy controls and the participants were therefore grouped together for subsequent analysis. Homozygocity for the minor C-allele of rs1801260 was associated with higher triglycerides (1.6 vs 1.2 mmol/L, P=0.03) together with higher fasting glucose (5.2 vs 4.7 mmol/L, P<0.001) and 120 min glucose (6.6 vs 5.4 mmol/L, P=0.04). There was no statistically significant association with HDL cholesterol (1.3 vs 1.5 mmo/L, P=0.09).

Conclusion: This study provides evidence that genetic variation in CLOCK is associated with abnormalities of lipid and glucose metabolism in premenopausal women, and supports a role for the circadian clock in the development of the metabolic syndrome. Further larger studies will be required to confirm this interesting association.

Declaration of interest: There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Funding: Declaration of Funding: This work was supported by the British Heart Foundation (FS/05/031).

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