Number of CAG repeats and mortality in middle aged and older men.


Journal

Clinical endocrinology
ISSN: 1365-2265
Titre abrégé: Clin Endocrinol (Oxf)
Pays: England
ID NLM: 0346653

Informations de publication

Date de publication:
12 2023
Historique:
revised: 07 08 2023
received: 15 04 2023
accepted: 10 08 2023
medline: 6 11 2023
pubmed: 18 9 2023
entrez: 18 9 2023
Statut: ppublish

Résumé

The androgen receptor (AR) mediates peripheral effects of testosterone. Previous data suggests an association between the number of CAG repeats in exon-1 of the AR gene and AR transcriptional activity. The aim of this analysis was to determine the association between the number of AR CAG repeats and all-cause mortality in men and the influence of testosterone level on the association. Follow-up data to 27 January 2018 were available for men aged 40-79 years recruited across six countries of the European Male Aging Study between 2003 and 2005. Cox proportional hazards modelling was used to determine the association between CAG repeat number/mortality. Results were expressed as hazard ratios (HR)/95% confidence intervals (CI). One thousand nine hundred and seventy-seven men were followed up. Mean baseline age was 60 ± 11.1 years. Mean duration of follow-up was 12.2 years. At follow up 25.1% of men had died. CAG repeat length ranged from 6 to 39, with the highest proportion of CAG repeat number at 21 repeats (16.4%). In a multivariable model, compared to men with 22-23 AR CAG repeats: for men with <22 and >23 AR CAG HR, 95% CI for mortality were, <22 CAG repeats 1.17 (0.93-1.49) and >23 CAG repeats 1.14 (0.88-1.47). In a post-hoc analysis, the association was significant for men in the lowest tertile of baseline testosterone (<14.2 nmol/L) with >23 CAG repeats: in the adjusted model for <22 and >23 CAG repeats, respectively, 1.49 (0.97-2.27) and 1.68 (1.06-2.67) versus 22-23 repeats. Our European-wide cohort data overall found no association of androgen receptor CAG repeat number and mortality in men. However, post hoc analysis suggested that an association might be present in men with lower baseline testosterone concentrations, which merits further investigation.

Identifiants

pubmed: 37718889
doi: 10.1111/cen.14962
doi:

Substances chimiques

Receptors, Androgen 0
Testosterone 3XMK78S47O

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

559-565

Informations de copyright

© 2023 The Authors. Clinical Endocrinology published by John Wiley & Sons Ltd.

Références

Heald A, Cook M, Antonio L, et al. The number of androgen receptor CAG repeats and mortality in men. Aging Male. 2022;25:167-172.
Heald AH, Yadegar Far G, Livingston M, et al. Androgen receptor-reduced sensitivity is associated with increased mortality and poorer glycaemia in men with type 2 diabetes mellitus: a prospective cohort study. Cardiovasc Endocrinol Metab. 2020;10:37-44.
Pye SR, Huhtaniemi IT, Finn JD, et al. EMAS Study Group. Late-onset hypogonadism and mortality in aging men. J Clin Endocrinol Metab. 2014;99:1357-1366.
Lee DM, O'Neill TW, Pye SR, et al. EMAS study group. The European Male Ageing Study (EMAS): design, methods and recruitment. Int J Androl. 2009;32:11-24.
Ketha H, Kaur S, Grebe SK, Singh RJ. Clinical applications of LC-MS sex steroid assays: evolution of methodologies in the 21st century. Curr Opin Endocrinol Diab Obes. 2014;21:217-226.
Vermeulen A, Verdonck L, Kaufman JM. A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab. 1999;84:3666-3672.
doi:10.1016/j.jsbmb.2006.02.004. Accessed January 5, 2023.
Nenonen HA, Giwercman A, Hallengren E, Giwercman YL. Non-linear association between androgen receptor CAG repeat length and risk of male subfertility-a meta-analysis. Int J Androl. 2011;34:327-332.
Gianatti EJ, Grossmann M. Testosterone deficiency in men with type 2 diabetes: pathophysiology and treatment. Diabetic Med. 2020;37:174-186.
Trzmiel-Bira A, Filus A, Kuliczkowska-Płaksej J, et al. The CAG repeat polymorphism in androgen receptor gene repeat and frequency of chosen parameters of metabolic syndrome in 45-65 aged men in Wroclaw population. Endokrynol Pol. 2008;59:477-482.
Zitzmann M, Gromoll J, von Eckardstein A, Nieschlag E. The CAG repeat polymorphism in the androgen receptor gene modulates body fat mass and serum concentrations of leptin and insulin in men. Diabetologia. 2003;46:31-39.
Zitzmann M, Nieschlag E. Androgen receptor gene CAG repeat length and body mass index modulate the safety of long-term intramuscular testosterone undecanoate therapy in hypogonadal men. J Clin Endocrinol Metab. 2007;92:3844-3853.
Haring R, Ernst F, Schurmann C, et al. The androgen receptor CAG repeat polymorphism as a risk factor of low serum testosterone and its cardiometabolic effects in men. Int J Androl. 2012;35:511-520.
Page ST, Kupelian V, Bremner WJ, McKinlay JB. The androgen receptor gene CAG repeat polymorphism does not predict increased risk of heart disease: longitudinal results from the Massachusetts male Ageing Study. Clin Endocrinol. 2006;65:333-339.
Hackett G, Heald AH, Sinclair A, Jones PW, Strange RC, Ramachandran S. Serum testosterone, testosterone replacement therapy and all-cause mortality in men with type 2 diabetes: retrospective consideration of the impact of PDE5 inhibitors and statins. Int J Clin Pract. 2016;70:244-253.
Stanworth RD, Kapoor D, Channer KS, Jones TH. Androgen receptor CAG repeat polymorphism is associated with serum testosterone levels, obesity and serum leptin in men with type 2 diabetes. Eur J Endocrinol. 2008;159:739-746.
Tirabassi G, Cignarelli A, Perrini S, et al. Influence of CAG repeat polymorphism on the targets of testosterone action. Int J Endocrinol. 2015;2015:1-12.
Stanworth RD, Kapoor D, Channer KS, Jones TH. Dyslipidaemia is associated with testosterone, oestradiol and androgen receptor CAG repeat polymorphism in men with type 2 diabetes. Clin Endocrinol. 2011;74:624-630.
Kelly DM, Jones TH. Testosterone and cardiovascular risk in men. Front Horm Res. 2014;43:1-20.

Auteurs

Adrian Heald (A)

Department of Endocrinology and Diabetes, Salford Royal Hospital, Salford, UK.
The School of Medicine and Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK.

Michael J Cook (MJ)

Centre for Health Informatics, Division of Informatics, Imaging and Data Science, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK.
National Institute for Health and Care Research Applied Research Collaboration Greater Manchester, Manchester, UK.

Leen Antonio (L)

Department of Endocrinology, University Hospitals Leuven, Leuven, Belgium.
Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium.

Jos Tournoy (J)

Department of Public Health and Primary Care, Gerontology and Geriatrics Unit, KU Leuven-University of Leuven, Leuven, Belgium.
Department of Geriatric Medicine, University Hospitals Leuven, Leuven, Belgium.

Parisa Ghaffari (P)

Department of Endocrinology and Diabetes, Salford Royal Hospital, Salford, UK.

Fahmida Mannan (F)

The School of Medicine and Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK.

Helene Fachim (H)

Department of Endocrinology and Diabetes, Salford Royal Hospital, Salford, UK.
The School of Medicine and Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK.

Dirk Vanderschueren (D)

Department of Endocrinology, University Hospitals Leuven, Leuven, Belgium.
Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium.

Ian Laing (I)

Department of Biochemistry, Royal Preston Hospital, Preston, UK.

Geoff Hackett (G)

Aston University Medical School, Birmingham, UK.

Felipe F Casanueva (FF)

Department of Medicine, Santiagode Compostela University, Complejo Hospitalario Universitariode Santiago (CHUS), CIBER de Fisiopatología Obesidady Nutricion (CB06/03), Instituto Salud Carlos III, Santiago de Compostela, Spain.

Ilpo T Huhtaniemi (IT)

Department of Metabolism, Institute of Reproductive and Developmental, Digestion and Reproduction, Imperial College London, London, UK.

Mario Maggi (M)

"Mario Serio" Department of Experimental and Clinical Biomedical Sciences, Endocrinology Unit, University of Florence, Florence, Italy.

Giulia Rastrelli (G)

"Mario Serio" Department of Experimental and Clinical Biomedical Sciences, Endocrinology Unit, University of Florence, Florence, Italy.

Jolanta Slowikowska-Hilczer (J)

Department of Andrology and Reproductive Endocrinology, Medical University of Łódź, Łódź, Poland.

Fred Wu (F)

The School of Medicine and Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK.
Department of Endocrinology, Manchester Royal Infirmary, The University of Manchester, Manchester, UK.

Terence W O'Neill (TW)

Centre for Epidemiology Versus Arthritis, The University of Manchester, Manchester, UK.
Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre, Salford, UK.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH