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

AbstractPolycystic ovary syndrome (PCOS) is a frequent heterogenic disorder with a familial background. Androgenic effects, determining the clinical features of the syndrome, are mediated by the androgen receptor (AR), whose activity is modulated by a genetic polymorphism. We investigated the role of the CAG repeat polymorphism of the androgen receptor in PCOS.In the infertility unit of a university clinic, 72 PCOS patients were compared with 179 ovulatory controls undergoing a standardized diagnostic work-up. The number of CAG repeats was determined by PCR, labelling with IR-800 and PAGE. X-chromosome inactivation was assessed by a methylation-sensitive assay.Compared to controls, PCOS patients displayed a shorter mean CAG repeat length, encoding for higher AR activity (P=0.001). CAG repeat length correlated inversely with oligomenorrhea, a central androgen dependent feature of the syndrome (P=0.005). In a binomial regression analysis including BMI, LH and free testosterone, CAG repeat length was identified as an independent risk factor for PCOS (P=0.002).The CAG repeat polymorphism could constitute one of the genetic factors modulating the syndrome’s phenotype, contributing to its clinical heterogeneity and associated metabolic consequences.

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Role of androgen receptor CAG repeat polymorphism length in hypothalamic progesterone sensitivity in hyperandrogenic adolescent girls

Endocrine ◽

10.1007/s12020-011-9563-1 ◽

2011 ◽

Vol 41 (1) ◽

pp. 156-158 ◽

Cited By ~ 1

Author(s):

Michelle Y. Abshire ◽

Susan K. Blank ◽

Sandhya Chhabra ◽

Christopher R. McCartney ◽

Christine A. Eagleson ◽

...

Keyword(s):

Androgen Receptor ◽

Adolescent Girls ◽

Cag Repeat ◽

Repeat Polymorphism

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Effectiveness of Gonadotropin Administration for Spermatogenesis Induction in Hypogonadotropic Hypogonadism: A Possible Role of Androgen Receptor CAG Repeat Polymorphism and Therapeutic Measures

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/187153012802002866 ◽

2012 ◽

Vol 12 (3) ◽

pp. 236-242 ◽

Cited By ~ 2

Author(s):

V. A. Giagulli ◽

V. Triggiani ◽

G. Corona ◽

M. D. Carbone ◽

E. Tafaro ◽

...

Keyword(s):

Androgen Receptor ◽

Hypogonadotropic Hypogonadism ◽

Cag Repeat ◽

Repeat Polymorphism ◽

Therapeutic Measures

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Role of the Androgen Receptor Gene CAG Repeat Polymorphism on the Sequence of Pubertal Events and Adiposity in Girls with High Dehydroepiandrosterone Sulfate Level

Journal of Pediatric and Adolescent Gynecology ◽

10.1016/j.jpag.2018.11.012 ◽

2019 ◽

Vol 32 (3) ◽

pp. 271-277

Author(s):

María Cecilia Lardone ◽

Andrea Castro ◽

Ana Pereira ◽

Camila Corvalán ◽

Eliana Ortíz ◽

...

Keyword(s):

Androgen Receptor ◽

Receptor Gene ◽

Dehydroepiandrosterone Sulfate ◽

Androgen Receptor Gene ◽

Cag Repeat ◽

Repeat Polymorphism

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The role of androgen receptor CAG repeat polymorphism and other factors which affect the clinical response to testosterone replacement in metabolic syndrome and type 2 diabetes: TIMES2 sub-study

Acta Endocrinologica ◽

10.1530/eje-13-0703 ◽

2014 ◽

Vol 170 (2) ◽

pp. 193-200 ◽

Cited By ~ 12

Author(s):

R D Stanworth ◽

S Akhtar ◽

K S Channer ◽

T H Jones

Keyword(s):

Type 2 Diabetes ◽

Metabolic Syndrome ◽

Androgen Receptor ◽

Clinical Response ◽

Cag Repeat ◽

Testosterone Replacement ◽

Outcome Variable ◽

Repeat Polymorphism

ContextThe TIMES2 (testosterone replacement in hypogonadal men with either metabolic syndrome or type 2 diabetes) study reported beneficial effects of testosterone replacement therapy (TRT) on insulin resistance and other variables in men with diabetes or metabolic syndrome. The androgen receptor CAG repeat polymorphism (AR CAG) is known to affect stimulated AR activity and has been linked to various clinically relevant variables.ObjectiveTo assess the role of AR CAG in the alteration of clinical response to TRT in the TIMES2 study.DesignSubgroup analysis from a multicentre, randomised, double-blind, placebo-controlled and parallel group study.SettingOutpatient study recruiting from secondary and primary care.PatientsA total of 139 men with hypogonadism and type 2 diabetes or metabolic syndrome, of which 73 received testosterone during the TIMES2 study.InterventionTestosterone 2% transdermal gel vs placebo.Main outcome measureRegression coefficient of AR CAG from linear regression models for each variable.ResultsAR CAG was independently positively associated with change in fasting insulin, triglycerides and diastolic blood pressure during TRT with a trend to association with HOMA-IR – the primary outcome variable. There was a trend to negative association between AR CAG and change in PSA. There was no association of AR CAG with change in other glycaemic variables, other lipid variables or obesity.ConclusionAR CAG affected the response of some variables to TRT in the TIMES2 study, although the association with HOMA-IR did not reach significance. Various factors may have limited the power of our study to detect the significant associations between AR CAG, testosterone levels and change in variables with testosterone treatment. Analysis of similar data sets from other clinical trials is warranted.

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