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The role of androgen receptor CAG repeat polymorphism in androgen excess disorder and idiopathic hirsutism

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Abstract

Purpose

The study aimed to investigate whether repeat number in the androgen receptor (AR) gene has any contribution to phenotypes of the disease of androgen excess (polycystic ovary syndrome (PCOS), idiopathic hyperandrogenemia (IHA) and idiopathic hirsutism (IH) in a cohort of Turkish women.

Methods

Three hundred and fifty-four voluntary premenopausal women (172 healthy controls and 182 patients with androgen excess disorders and idiopathic hirsutism) 18–45 years of age seen at an outpatient endocrine clinic at Erciyes University Hospital between January 2013 and December 2014 were included. All volunteers have undergone physical examination and biochemical evaluation. The polymorphic (CAG)n repeat of the human AR was determined by fragment analyses.

Results

Detailed clinical analyses of the patients ended up with 137 PCOS, 24 IHA, and 21 IH. Pairwise comparisons revealed the CAG repeat number differences between the PCOS and controls (p = 0.005) and IH and controls (p = 0.020). Women with CAG repeat length ≤ 17 had a significantly increased twofold risk for PCOS than those women with > 17 CAG repeats OR: 2.0 (95% CI 1.2–3.3, p = 0.005). Women with CAG repeat length ≤ 17 had a significantly increased threefold risk for IH than those women with > 17 CAG repeats OR: 2.9 (95% CI 1.2–7.3, p = 0.020). When correlation analysis was performed, a weak negative correlation was detected between the short allele and FGS score (r = − 0.131, p = 0.013) and a positive relationship between total testosterone and longer allele in the IHA group (r = 0.425, p = 0.039). Median repeat length of the shorter allele between oligomenorrhea and woman with normal menstrual cycle was found to be statistically significant (p = 0.017).

Conclusion

This study indicated that the risk of PCOS and IH is associated with the inheritance of ARs with shorter CAG repeats.

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Funding

This work was supported by the Scientific Research Projects Coordination Unit of Erciyes University. Grand Number: TDK-2014–5099.

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The study was approved by the Ethics Committee of Medical School at Erciyes University. All procedures performed in studies involving human participants and/or animals were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Polat, S., Karaburgu, S., Unluhizarci, K. et al. The role of androgen receptor CAG repeat polymorphism in androgen excess disorder and idiopathic hirsutism. J Endocrinol Invest 43, 1271–1281 (2020). https://doi.org/10.1007/s40618-020-01215-7

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