Abstract


Introduction: The Androgen Receptor (AR) tri-nucleotide CAG repeat length polymorphism has been proposed to be a genetic determinant of between-individual variations in androgen action on target tissue (1-9). However, most previous studies have been cross-sectional in design from single centres. Multi-centre studies investigating longitudinal changes in androgen–responsive endpoints (AREs) in relation to the AR CAG repeat length are lacking. view more

Introduction: The Androgen Receptor (AR) tri-nucleotide CAG repeat length polymorphism has been proposed to be a genetic determinant of between-individual variations in androgen action on target tissue (1-9). However, most previous studies have been cross-sectional in design from single centres. Multi-centre studies investigating longitudinal changes in androgen–responsive endpoints (AREs) in relation to the AR CAG repeat length are lacking.
Aim and setting: The aim of the study was to assess whether the AR CAG repeat length is associated with longitudinal change in AREs in a multi-center European cohort study of middle-aged and elderly men (10-11).
Methods: 2228 men (mean±sd age at follow-up: 63±11 years) from 8 European countries comprised the analysis sample after exclusion of those with diagnosed diseases of the hypothalamic-pituitary-gonadal (HPG) axis. Phenotypic assessments undertaken included AREs, such as reproductive hormone levels, body composition, carbohydrate metabolism, hematological and cognitive parameters, and self-reported physical activity, sexual, physical and psychological symptoms and medical conditions. Follow-up measurements were performed a median of 4.3 years later. The AR CAG repeat length was measured using fluorescently-labeled PCR (12). The longitudinal association between relative change in AREs from baseline (dependent variables) and the AR CAG repeat length (independent variable) was assessed using regression analysis adjusting for age and center. The AR CAG repeat length was treated as a continuous linear and also categorical (6-20; 21-23; 24-39 repeats) predictor.
Results: The distribution of the AR CAG repeat length (6-20: 581 men, 21-23: 667 men, 24-39: 639 men) was similar to previous studies in community-dwelling European men (9). Analysis of the AR CAG repeat length as a linear predictor of relative change in AREs revealed no significant associations after adjustment: overall sexual function (β:-0.01, 95%CI:-0.07;0.04), hemoglobin (β:-0.02, 95%CI:-0.07;0.03), estimated bone mineral density (β:0.01, 95%CI:-0.04;0.05), waist circumference (β:-0.04, 95%CI:-0.08;0.01), HOMA-IR (β:0.01, 95%CI:-0.04;0.06) and physical performance (β:-0.02, 95%CI:-0.07;0.02). Similar results were obtained, when the AR CAG repeat length was categorized into 3 groups.  
Conclusion: In this prospective study of community-dwelling middle-aged and elderly men, the AR CAG repeat length was not associated with changes in AREs. We conclude that in individuals with a functional HPG axis, variations in the AR CAG repeat length do not appear to impact on short-term changes in androgen-related physiological endpoints in the general population.

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