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

Design: 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 rep...

Full description

Bibliographic Details
Authors: Heald, A.; Cook, M.J.; Antonio, L.; Tournoy, J.; Ghaffari, P.; Mannan, F.; Fachim, H.; Vanderschueren, D.; Laing, I.; Hackett, G.; Casanueva Freijo, Felipe; Huhtaniemi, I.T.; Maggi, M.; Rastrelli, G.; Slowikowska-Hilczer, J.; Wu, F.; O'Neill, T.W.
Format: Article
Publication date:2023
Country:España
Institution:Servizo Galego de Saúde (SERGAS)
Repository:RUNA. Repositorio da Consellería de Sanidade e Sergas
OAI Identifier:oai:runa.sergas.gal:20.500.11940/21794
Online Access:https://portalcientifico.sergas.gal//documentos/651014aa0058624993e2cdf9
http://hdl.handle.net/20.500.11940/21794
Access Level:Open access
Keyword:Humans
Middle Aged
Male
Aged
Receptors, Androgen
Trinucleotide Repeats
Aging
Testosterone
AS Santiago
IDIS
_version_ 1878730215012696064
author Heald, A.
author2 Cook, M.J.
Antonio, L.
Tournoy, J.
Ghaffari, P.
Mannan, F.
Fachim, H.
Vanderschueren, D.
Laing, I.
Hackett, G.
Casanueva Freijo, Felipe
Huhtaniemi, I.T.
Maggi, M.
Rastrelli, G.
Slowikowska-Hilczer, J.
Wu, F.
O'Neill, T.W.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author_browse Antonio, L.
Casanueva Freijo, Felipe
Cook, M.J.
Fachim, H.
Ghaffari, P.
Hackett, G.
Heald, A.
Huhtaniemi, I.T.
Laing, I.
Maggi, M.
Mannan, F.
O'Neill, T.W.
Rastrelli, G.
Slowikowska-Hilczer, J.
Tournoy, J.
Vanderschueren, D.
Wu, F.
author_facet Heald, A.
Cook, M.J.
Antonio, L.
Tournoy, J.
Ghaffari, P.
Mannan, F.
Fachim, H.
Vanderschueren, D.
Laing, I.
Hackett, G.
Casanueva Freijo, Felipe
Huhtaniemi, I.T.
Maggi, M.
Rastrelli, G.
Slowikowska-Hilczer, J.
Wu, F.
O'Neill, T.W.
author_role author
collection RUNA. Repositorio da Consellería de Sanidade e Sergas
description Design: 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. Patients and Measurements: 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). Results: 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. Conclusions: 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.
eu_rights_str_mv openAccess
format article
id ES_17cc2e1ccc6dacfb2be4090cf9b5ea34
institution Servizo Galego de Saúde (SERGAS)
instname_str Servizo Galego de Saúde (SERGAS)
network_acronym_str ES
network_name_str España
oai_identifier_str oai:runa.sergas.gal:20.500.11940/21794
publishDate 2023
publishDateSort 2023
reponame_str RUNA. Repositorio da Consellería de Sanidade e Sergas
spelling Number of CAG repeats and mortality in middle aged and older men Heald, A. Cook, M.J. Antonio, L. Tournoy, J. Ghaffari, P. Mannan, F. Fachim, H. Vanderschueren, D. Laing, I. Hackett, G. Casanueva Freijo, Felipe Huhtaniemi, I.T. Maggi, M. Rastrelli, G. Slowikowska-Hilczer, J. Wu, F. O'Neill, T.W. Humans Middle Aged Male Aged Receptors, Androgen Trinucleotide Repeats Aging Testosterone AS Santiago IDIS Design: 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. Patients and Measurements: 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). Results: 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. Conclusions: 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. https://portalcientifico.sergas.gal//documentos/651014aa0058624993e2cdf9 http://hdl.handle.net/20.500.11940/21794
spellingShingle Number of CAG repeats and mortality in middle aged and older men
Heald, A.
Humans
Middle Aged
Male
Aged
Receptors, Androgen
Trinucleotide Repeats
Aging
Testosterone
AS Santiago
IDIS
title Number of CAG repeats and mortality in middle aged and older men
title_full Number of CAG repeats and mortality in middle aged and older men
title_fullStr Number of CAG repeats and mortality in middle aged and older men
title_full_unstemmed Number of CAG repeats and mortality in middle aged and older men
title_short Number of CAG repeats and mortality in middle aged and older men
title_sort Number of CAG repeats and mortality in middle aged and older men
topic Humans
Middle Aged
Male
Aged
Receptors, Androgen
Trinucleotide Repeats
Aging
Testosterone
AS Santiago
IDIS
topic_facet Humans
Middle Aged
Male
Aged
Receptors, Androgen
Trinucleotide Repeats
Aging
Testosterone
AS Santiago
IDIS
url https://portalcientifico.sergas.gal//documentos/651014aa0058624993e2cdf9
http://hdl.handle.net/20.500.11940/21794