Shortened Relative Leukocyte Telomere Length Is Associated With Polycystic Ovary Syndrome and Metabolic Traits

IF 2.7 Q3 ENDOCRINOLOGY & METABOLISM Endocrinology, Diabetes and Metabolism Pub Date : 2025-02-18 DOI:10.1002/edm2.70030

Raymond N.C. Chan, Chuiguo Huang, Noel Y. H. Ng, Henry C. H. Tam, Claudia H. T. Tam, Feifei Cheng, Kwun Kiu Wong, Mai Shi, Alex C. W. Ng, Atta Y. T. Tsang, Chi Chiu Wang, Lai Ping Cheung, Wing Hung Tam, Mugdha V. Joglekar, Anandwardhan A. Hardikar, Alicia J. Jenkins, Juliana C. N. Chan, Cadmon K. P. Lim, Ronald C. W. Ma

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Abstract

Background

Polycystic ovary syndrome (PCOS) is one of the commonest gyneco-endocrine disorders amongst women of reproductive age. Whether PCOS and cardiometabolic traits in PCOS patients are associated with shortened telomere length (TL) or relative leukocyte telomere length (rLTL) remains unclear.

Methods

214 women with PCOS and 214 age-matched women were recruited. rLTL was measured with an updated quantitative real-time PCR protocol and reported as ΔΔCt between telomere and a single-copy gene encoding β-globin relative to a normalisation control. A two-way Mendelian randomization analysis using the UK Biobank Resource was performed to assess the causal relationship between rLTL and PCOS.

Results

Women with PCOS had significantly shortened rLTL (PCOS: 0.5 ± 0.7; control: 0.8 ± 0.6; p < 0.001). Longer rLTL was associated with a lower risk of PCOS after adjusting for age, history of smoking and other cardiometabolic traits (OR: 0.503; 95% CI: 0.342–0.730; p < 0.001). Longer rLTL was associated with reduced risk of dyslidpidemia (OR: 0.563; 95% CI: 0.450–0.968; p = 0.042) in PCOS patients. PCOS subjects with rLTL shorter than mean of the rLTL of control subjects had an elevated risk of dysglycemia (OR: 2.09; 95% CI: 1.04–4.29; p = 0.040). No causal relationships were found between rLTL and PCOS in the Mendelian randomization study.

Conclusions

Women with PCOS have significantly reduced rLTL and shorter LTL may be associated with cardiometabolic risk factors in PCOS subjects. There are no causal relationship between genetically determined PCOS and TL or vice versa.

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