Robert J A H Eendebak1, Ilpo T Huhtaniemi2, Stephen R Pye3, Tomas Ahern4, Terence W O'Neill3, György Bartfai5, Felipe F Casanueva6, Mario Maggi7, Gianni Forti7, Robert D Alston4, Aleksander Giwercman8, Thang S Han9, Krzysztof Kula10, Michael E J Lean11, Margus Punab12, Neil Pendleton13, Brian G Keevil14, Dirk Vanderschueren15, Martin K Rutter16,17, Gindo Tampubolon18, Royston Goodacre19, Frederick C W Wu4. 1. Faculty of Medical and Human SciencesInstitute of Human Development, Centre for Endocrinology and Diabetes, Andrology Research Unit, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK roberteendebak@gmail.com. 2. Department of Surgery and CancerInstitute of Reproductive and Developmental Biology, Imperial College London, London, UK. 3. Arthritis Research UK Centre for EpidemiologyCentre for Musculoskeletal Health, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK. 4. Faculty of Medical and Human SciencesInstitute of Human Development, Centre for Endocrinology and Diabetes, Andrology Research Unit, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK. 5. Department of Obstetrics and Gynaecology and AndrologyAlbert Svent Gyorgy Medical University, Szeged, Hungary. 6. Department of MedicineUniversity Santiago de Compostela, Santiago de Compostela, UK. 7. Department of Clinical PhysiopathologyAndrology Unit, University of Florence, Florence, Italy. 8. Department of UrologyScanian Andrology Centre, Malmo University Hospital, Lund University, Malmo, Sweden. 9. Department of EndocrinologyUniversity College London, London, UK. 10. Department of Andrology and Reproductive EndocrinologyMedical University Lodz, Lodz, Poland. 11. Department of Human NutritionUniversity of Glasgow, Glasgow, UK. 12. United LabsAndrology Unit, Tartu University Clinic, Tartu, Estonia. 13. Salford Royal NHS TrustSchool of Community Based Medicine, University of Manchester, Manchester, UK. 14. Department of Clinical BiochemistryUniversity South Manchester Hospital, Manchester, UK. 15. Department of Andrology and EndocrinologyCatholic University Leuven, Leuven, Belgium. 16. Manchester Diabetes CentreCentral Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Sciences Centre. 17. Faculty of Medical and Human SciencesInstitute of Human Development, Endocrinology and Diabetes Research Group. 18. Faculty of HumanitiesCathie Marsh Institute for Social Research. 19. School of ChemistryManchester Institute for Biotechnology, University of Manchester, Manchester, UK.
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 that are influenced by testosterone (T) levels in middle-aged and elderly European men. DESIGN: Multinational European observational prospective cohort study. PARTICIPANTS: A total of 1887 men (mean ± s.d. age: 63 ± 11 years; median follow up: 4.3 years) from centres of eight 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 as both a continuous and a 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 a 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 time frame, variations in the AR CAG repeat do not contribute to the rate of phenotypic ageing, over and above, which might be associated with the age-related decline in T levels.
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 that are influenced by testosterone (T) levels in middle-aged and elderly European men. DESIGN: Multinational European observational prospective cohort study. PARTICIPANTS: A total of 1887 men (mean ± s.d. age: 63 ± 11 years; median follow up: 4.3 years) from centres of eight 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 as both a continuous and a 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 a 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 time frame, variations in the AR CAG repeat do not contribute to the rate of phenotypic ageing, over and above, which might be associated with the age-related decline in T levels.
Authors: Angela K Lucas-Herald; Rheure Alves-Lopes; Augusto C Montezano; S Faisal Ahmed; Rhian M Touyz Journal: Clin Sci (Lond) Date: 2017-07-01 Impact factor: 6.124