The androgen receptor gene CAG repeat in relation to 4-year changes in androgen-sensitive endpoints in community-dwelling older European men

Robert J.A.H. Eendebak, Ilpo Huhtaniemi, Stephen Pye, Tomas Ahern, Terence W. O'Neill, Georgy Bartfai, Felipe Casanueva, Mario Maggi, Gianni Forti, Robert Alston, Aleksander Giwercman, Thang S Han, Krzysztof Kula, Michael E J Lean, Margus Punab, Neil Pendleton, Brian Keevil, Dirk Vanderschueren, Martin Rutter, Gindo TampubolonRoyston Goodacre, Frederick Wu

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Abstract

Context: The Androgen Receptor (AR) gene exon 1 CAG repeat length has been proposed to be a determinant of between-individual variations in androgen action in target tissues, which might regulate phenotypic differences of human ageing. However, findings on its phenotypic effects are inconclusive.

Objective: To assess whether the AR CAG repeat length is associated with longitudinal changes in endpoints which are influenced by testosterone (T) levels in middle-aged and elderly European men.

Design: Multinational European observational prospective cohort study

Participants: 1887 men (mean±sd age: 63±11 years; median follow-up: 4.3 years) from centres of 8 European countries comprised the analysis sample after exclusion of those with diagnosed diseases of the hypothalamic-pituitary-testicular (HPT) axis.

Main outcome measures: Longitudinal associations between the AR CAG repeat and changes in androgen-sensitive endpoints (ASEs) and medical conditions were assessed using regression analysis adjusting for age and centre. The AR CAG repeat length was treated both as a continuous and categorical (6-20; 21-23; 24-39 repeats) predictor. Additional analysis investigated whether results were independent of baseline T or oestradiol (E2) levels.

Results: The AR CAG repeat, when used as a continuous or categorical predictor, was not associated with longitudinal changes in ASEs or medical conditions after adjustments. These results were independent of T and E2 levels.

Conclusion: Within a 4-year timeframe, variations in the AR CAG repeat do not contribute to the rate of phenotypic ageing, over and above, that, which might be associated with the age-related decline in T levels.
Original languageEnglish
Pages (from-to) 583-593
JournalEuropean Journal of Endocrinology
Volume175
Early online date15 Sept 2016
DOIs
Publication statusPublished - 1 Dec 2016

Keywords

  • Androgen receptor
  • Androgen action
  • Gonadal axis
  • Ageing
  • Genetics

Research Beacons, Institutes and Platforms

  • Cancer
  • Global inequalities

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