scholarly journals Is the effect of testosterone on body composition modulated by the androgen receptor gene CAG repeat polymorphism in elderly men?

2007 ◽  
Vol 156 (3) ◽  
pp. 395-401 ◽  
Author(s):  
B Lapauw ◽  
S Goemaere ◽  
P Crabbe ◽  
J M Kaufman ◽  
J B Ruige
Keyword(s):  
Body Composition ◽  
Androgen Receptor ◽  
Effect Modification ◽  
Community Dwelling ◽  
Repeat Length ◽  
Fat Free Mass ◽  
Cag Repeat ◽  
Repeat Polymorphism ◽  
Elderly Men ◽  
Body Composition Assessment

Objective: The androgen receptor (AR) gene contains a CAG repeat polymorphism coding for a polyglutamine chain, the length of which is inversely correlated with AR transcriptional activity. We explored whether this polymorphism modulates the activities of testosterone (T) related to body composition in elderly men. Design: We performed cross-sectional analyses using data from a 4-year follow-up study in community-dwelling men aged 75–89 years (n=159). Methods: Body composition was assessed by dual-energy X-ray absorptiometry and its relation with T and the AR gene CAG repeat length was assessed by multiple linear regression analyses, adjusting for confounding and exploring effect modification. Results: AR gene CAG repeat length was not directly related to body composition, either with or without adjustment for confounding variables like age, weight, total T or sex hormone binding globulin (SHBG) levels. However, exploration of effect modification showed that CAG repeat length modulated the relation between T and body composition (standardized regression coefficients of interaction term: β=0.12, P<0.01 and β=−0.09, P<0.05 for fat-free mass and fat mass respectively). These results were confirmed using similar models and data of mean T, SHBG and weight of the 2 years’ preceding body composition assessment instead of data of the same year (β=0.09, P<0.05 and β=−0.09, P<0.05 respectively). Conclusion: These findings suggest that the AR gene CAG polymorphism contributes, albeit modestly, to the between-subject variation of T action on body composition in community-dwelling elderly men.

Androgen receptor CAG repeat polymorphism is associated with fat-free mass in men

2005 ◽  
Vol 98 (1) ◽  
pp. 132-137 ◽  
Author(s):  
Sean Walsh ◽  
Joseph M. Zmuda ◽  
Jane A. Cauley ◽  
Patrick R. Shea ◽  
E. Jeffrey Metter ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Serum Testosterone ◽  
Fat Free Mass ◽  
Cag Repeat ◽  
Cag Repeats ◽  
Whole Body ◽  
Repeat Polymorphism ◽  
Repeat Number ◽  
Caucasian Men ◽  
Exon 1

The human androgen receptor (AR) gene contains a CAG (glutamine) repeat polymorphism in exon 1 that is inversely associated with transcriptional activity of the AR. We studied the association of AR CAG repeat length, fat-free mass (FFM), and testosterone in two independent cohorts: 294 Caucasian men, aged 55–93 yr, from the Study of Osteoporotic Risk in Men (STORM), and 202 Caucasian volunteers (112 men and 90 women), aged 19–90 yr, from the Baltimore Longitudinal Study of Aging (BLSA). Subjects were genotyped to determine the number of AR CAG repeats and grouped as carrying either <22 or ≥22 repeats. Whole body soft tissue composition was measured by dual-energy X-ray absorptiometry. Men with greater CAG repeat number exhibited significantly greater total FFM than those with fewer CAG repeats in both cohorts (STORM: 59.2 ± 0.3 vs. 58.0 ± 0.4 kg, P = 0.02; BLSA: 57.2 ± 1.1 vs. 53.8 ± 1.1 kg, P = 0.04). Similar results were observed for total FFM normalized to height. No differences were seen in women in the BLSA cohort. In the BLSA cohort, serum testosterone levels were higher in subjects with greater repeat number ( P = 0.003). This same pattern approached significance in the STORM cohort ( P = 0.07). In conclusion, the androgen receptor CAG repeat polymorphism is associated with FFM in men in two independent cohorts. Additional studies are needed to confirm this observation and to clarify the mechanisms involved.

scholarly journals Comparison of Body Composition Assessment Methods in Patients with Human Immunodeficiency Virus-Associated Wasting Receiving Growth Hormone

2006 ◽  
Vol 91 (8) ◽  
pp. 2952-2959 ◽  
Author(s):  
John G. Esposito ◽  
Scott G. Thomas ◽  
Lori Kingdon ◽  
Shereen Ezzat
Keyword(s):  
Body Composition ◽  
Bioelectrical Impedance ◽  
Community Dwelling ◽  
Fat Free Mass ◽  
Daily Injection ◽  
Crossover Fashion ◽  
Treatment Change ◽  
Body Composition Assessment ◽  
Before And After ◽  
Rhgh Treatment

Abstract Context: Bioelectrical impedance spectroscopy (BIS) and skinfold anthropometry (SKF) have been used to monitor body composition among patients with HIV wasting; however, validation of these techniques during recombinant human GH (rhGH) treatment has not been performed. Objective: Our objective was to evaluate the degree of agreement between criterion measurements of dual-energy x-ray absorptiometry (DXA) and those of BIS and SKF in patients with HIV wasting treated with rhGH. Design and Setting: We conducted a randomized, double-blinded, placebo-controlled, two-period crossover trial at the University of Toronto and Mount Sinai Hospital (Toronto, Canada). Patients: A referred sample of 27 community-dwelling men with HIV-associated weight loss (≥10% over preceding 12 months) despite optimal antiretroviral therapy participated in the study. Intervention: Intervention was one daily injection of rhGH (6 mg) or placebo self-administered for 3 months in a crossover fashion with a 3-month washout. Main Outcome Measures: Fat-free mass (FFM) and fat mass (FM) were measured by BIS, SKF, and DXA before and after rhGH and placebo treatment. Results: FFMBIS was not significantly different from FFMDXA after rhGH treatment (P = 0.10). Mean differences (bias ± sd) according to Bland-Altman analysis were smaller for SKF than for BIS (P &lt; 0.05) at all time points, yet treatment-induced change in FM was better detected with BIS than with SKF. BIS estimates of FFM and FM showed better agreement with those of DXA after rhGH treatment (1.6 ± 4.6 kg and −2.1 ± 3.9 kg) compared with baseline (3.8 ± 3.5 kg and −4.1 ± 3.6 kg) and placebo (2.7 ± 4.4 kg and −3.1 ± 4.6) (P &lt; 0.05). BIS overestimated and SKF underestimated the treatment-induced changes in FFM and FM. Conclusions: SKF was more accurate than BIS when measuring body composition in patients with HIV wasting before and after rhGH treatment; nonetheless, the accuracy of BIS increased after treatment. Change in FM because of treatment was not accurately assessed with SKF.

Role of the CAG Repeat Polymorphism of the Androgen Receptor Gene in Polycystic Ovary Syndrome (PCOS)

2011 ◽  
Vol 120 (02) ◽  
pp. 73-79 ◽  
Author(s):  
A. Schüring ◽  
A. Welp ◽  
J. Gromoll ◽  
M. Zitzmann ◽  
B. Sonntag ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Receptor Gene ◽  
Repeat Length ◽  
Cag Repeat ◽  
Cag Repeats ◽  
Repeat Polymorphism ◽  
Ovary Syndrome

AbstractPolycystic ovary syndrome (PCOS) is a frequent heterogenic disorder with a familial background. Androgenic effects, determining the clinical features of the syndrome, are mediated by the androgen receptor (AR), whose activity is modulated by a genetic polymorphism. We investigated the role of the CAG repeat polymorphism of the androgen receptor in PCOS.In the infertility unit of a university clinic, 72 PCOS patients were compared with 179 ovulatory controls undergoing a standardized diagnostic work-up. The number of CAG repeats was determined by PCR, labelling with IR-800 and PAGE. X-chromosome inactivation was assessed by a methylation-sensitive assay.Compared to controls, PCOS patients displayed a shorter mean CAG repeat length, encoding for higher AR activity (P=0.001). CAG repeat length correlated inversely with oligomenorrhea, a central androgen dependent feature of the syndrome (P=0.005). In a binomial regression analysis including BMI, LH and free testosterone, CAG repeat length was identified as an independent risk factor for PCOS (P=0.002).The CAG repeat polymorphism could constitute one of the genetic factors modulating the syndrome’s phenotype, contributing to its clinical heterogeneity and associated metabolic consequences.

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

2016 ◽  
Vol 175 (6) ◽  
pp. 583-593 ◽  
Author(s):  
Robert J A H Eendebak ◽  
Ilpo T Huhtaniemi ◽  
Stephen R Pye ◽  
Tomas Ahern ◽  
Terence W O’Neill ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Receptor Gene ◽  
Time Frame ◽  
Androgen Receptor Gene ◽  
Community Dwelling ◽  
Repeat Length ◽  
Cag Repeat ◽  
Medical Conditions ◽  
Longitudinal Changes ◽  
Age Related

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.

Androgen receptor gene CAG repeat polymorphism in longitudinal height and body composition in children and adolescents

2011 ◽  
Vol 74 (6) ◽  
pp. 732-735 ◽  
Author(s):  
Paul G. Voorhoeve ◽  
Willem van Mechelen ◽  
André G. Uitterlinden ◽  
Henriette A. Delemarre-van de Waal ◽  
Steven W. J. Lamberts
Keyword(s):  
Body Composition ◽  
Androgen Receptor ◽  
Children And Adolescents ◽  
Receptor Gene ◽  
Androgen Receptor Gene ◽  
Cag Repeat ◽  
Repeat Polymorphism

scholarly journals Endogenous hormones, androgen receptor CAG repeat length and fluid cognition in middle-aged and older men: results from the European Male Ageing Study

2010 ◽  
Vol 162 (6) ◽  
pp. 1155-1164 ◽  
Author(s):  
David M Lee ◽  
Aslan Ulubaev ◽  
Abdelouahid Tajar ◽  
Stephen R Pye ◽  
Neil Pendleton ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Free Testosterone ◽  
Community Dwelling ◽  
Repeat Length ◽  
Cag Repeat ◽  
Sex Hormone Binding Globulin ◽  
Gas Chromatography Mass Spectrometry ◽  
Total Testosterone ◽  
Endogenous Hormones ◽  
Health Lifestyle

ObjectiveData remain divergent regarding the activational effects of endogenous hormones on adult cognitive function. We examined the association between cognition, hormones and androgen receptor (AR) CAG repeat length in a large cohort of men.DesignCommunity-based, cross-sectional study of 3369 men aged 40–79 years.MethodsCognition tests were the Rey-Osterrieth Complex Figure, Camden Topographical Recognition Memory and Digit-Symbol Substitution. A fluid cognition (FC) z-score was computed from the individual tests. Testosterone, oestradiol (OE2) and 5α-dihydrotestosterone were measured by gas chromatography–mass spectrometry; DHEAS, LH, FSH and sex hormone-binding globulin (SHBG) by electrochemiluminescence. Free testosterone and OE2 were calculated from total hormone, SHBG and albumin. CAG repeat lengths were assayed by PCR genotyping.ResultsTotal testosterone and free testosterone were associated with higher FC z-scores, LH and FSH with lower FC z-scores in age-adjusted linear regressions. After adjusting for health, lifestyle and centre, a modest association was only observed between DHEAS and a lower FC z-score (β=−0.011, P=0.02), although this was driven by subjects with DHEAS levels >10 μmol/l. Locally weighted plots revealed no threshold effects between hormones and FC. There was no association between CAG repeat length and FC z-score after adjustment for age and centre (β=−0.007, P=0.06), nor any interaction effect between CAG repeat length and hormones.ConclusionOur results suggest that endogenous hormones are not associated with a vision-based measure of FC among healthy, community-dwelling men. Further studies are warranted to determine whether ‘high’ DHEAS levels are associated with poorer performance on a broader range of neuropsychological tests.

Genetic Screening in Infertile Mexican Men: Chromosomal Abnormalities, Y Chromosome Deletions, and Androgen Receptor CAG Repeat Length

2008 ◽  
Vol 29 (6) ◽  
pp. 654-660 ◽  
Author(s):  
S. G. Martinez-Garza ◽  
M. C. Gallegos-Rivas ◽  
M. Vargas-Maciel ◽  
J. M. Rubio-Rubio ◽  
M. E. de los Monteros-Rodriguez ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Y Chromosome ◽  
Genetic Screening ◽  
Chromosomal Abnormalities ◽  
Repeat Length ◽  
Cag Repeat ◽  
Chromosome Deletions ◽  
Mexican Men

Association Between Androgen Receptor Gene CAG Repeat Polymorphism and Plasma Testosterone Levels in Postmenopausal Women

2005 ◽  
Vol 12 (2) ◽  
pp. 135-141 ◽  
Author(s):  
Ilma Simoni Brum ◽  
Poli Mara Spritzer ◽  
Franyoise Paris ◽  
Maria Augusta Maturana ◽  
Franyoise Audran ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Postmenopausal Women ◽  
Receptor Gene ◽  
Androgen Receptor Gene ◽  
Cag Repeat ◽  
Plasma Testosterone ◽  
Repeat Polymorphism ◽  
Testosterone Levels
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