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 Cag Repeat Number in Androgen Receptor Gene and Male Infertility

2007 ◽  
Vol 10 (1) ◽  
pp. 19-24 ◽  
Author(s):  
T Plaseski ◽  
P Noveski ◽  
C Dimitrovski ◽  
B Kocevska ◽  
G Efremov ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Male Infertility ◽  
Receptor Gene ◽  
Androgen Receptor Gene ◽  
Cag Repeat ◽  
Cag Repeats ◽  
Control Group ◽  
Repeat Number ◽  
Number Of Patients ◽  
Exon 1

Cag Repeat Number in Androgen Receptor Gene and Male InfertilityAndrogens are essential for male sexual development and for fertility. They exert their action through the androgen receptor (AR), a ligandactivated transcription factor. The 5' end of exon 1 of the AR gene includes a polymorphic CAG triplet repeat that varies in number between 10 to 36 in the normal population. There is controversy over an association between high CAG repeat numbers in the AR gene and male infertility. We have evaluated the possible effect of long CAG repeats in the AR on infertility in men from the Republic of Macedonia (R. Macedonia). A group of 222 infertile/subfertile males with different sperm counts and a control group of 152 proven fathers were studied. The CAG repeat number was determined by fluorescent polymerase chain reaction (PCR) amplification of exon 1 of the AR gene analyzed by capillary electrophoresis. Mean CAG length did not differ significantly between males with azoospermia (22.0 ± 3.1), mild oligozoospermia (22.4 ± 2.6), severe oligozoospermia (23.0 ± 4.2), normozoospermia (21.8 ± 2.4), or known causes of infertility (22.1 ± 2.9) and fertile controls (22.3 ± 2.9). However, we found a significantly higher percentage of CAG repeats >26 (p = 0.022), >27 (p = 0.018) and >28 (p = 0.009) in males with mild oligozoospermia. These results indicate a possible association between CAG repeat length and mild oligozoospermia. Further studies on a larger number of patients with mild oligozoospermia are warranted to confirm this association.

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.

scholarly journals Polymorphisms of the Androgen Receptor Gene and the Estrogen Receptor β Gene Are Associated with Androgen Levels in Women1

2001 ◽  
Vol 86 (6) ◽  
pp. 2562-2568 ◽  
Author(s):  
Lars Westberg ◽  
Fariba Baghaei ◽  
Roland Rosmond ◽  
Monika Hellstrand ◽  
Mikael Landén ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Androgen Receptor ◽  
Receptor Gene ◽  
Premenopausal Women ◽  
Cag Repeat ◽  
Cag Repeats ◽  
Total Testosterone ◽  
Repeat Polymorphism ◽  
Ca Repeat ◽  
Androgen Levels

To elucidate the possible role of genetic variation in androgen receptor (AR), estrogen receptor α (ERα), and ERβ on serum androgen levels in premenopausal women, the CAG repeat polymorphism of the AR gene, the TA repeat polymorphism of the ERα gene, and the CA repeat polymorphism of the ERβ gene were studied in a population-based cohort of 270 women. Total testosterone, free testosterone, dehydroepiandrosterone sulfate, androstenedione, 17-hydroxyprogesterone, 3α-androstanediol glucuronide, 17β-estradiol, LH, FSH, and sex steroid hormone-binding globulin (SHBG) were measured in serum samples obtained in the follicular phase of the menstrual cycle. Women with relatively few CAG repeats in the AR gene, resulting in higher transcriptional activity of the receptor, displayed higher levels of serum androgens, but lower levels of LH, than women with longer CAG repeat sequences. The CA repeat of the ERβ gene also was associated with androgen and SHBG levels; women with relatively short repeat regions hence displayed higher hormone levels and lower SHBG levels than those with many CA repeats. In contrast, the TA repeat of the ERα gene was not associated with the levels of any of the hormones measured. Our results suggest that the serum levels of androgens in premenopausal women may be influenced by variants of the AR gene and the ERβ gene, respectively.

scholarly journals Cag Repeat Number in the Androgen Receptor Gene and Prostate Cancer

2012 ◽  
Vol 15 (1) ◽  
pp. 31-36 ◽  
Author(s):  
S Madjunkova ◽  
A Eftimov ◽  
V Georgiev ◽  
D Petrovski ◽  
A Dimovski ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Cancer Risk ◽  
Receptor Gene ◽  
Prostate Cancer Risk ◽  
Androgen Receptor Gene ◽  
Repeat Length ◽  
Cag Repeat ◽  
Cag Repeats ◽  
Repeat Number

Cag Repeat Number in the Androgen Receptor Gene and Prostate CancerProstate cancer (PC) is the second leading cause of cancer deaths in men. The effects of androgens on prostatic tissue are mediated by the androgen receptor (AR) gene. The 5' end of exon 1 of the AR gene includes a polymorphic CAG triplet repeat that numbers between 10 to 36 in the normal population. The length of the CAG repeats is inversely related to the transactivation function of the AR gene. There is controversy over association between short CAG repeat numbers in the AR gene and PC. This retrospective case-control study evaluates the possible effect of short CAG repeats on the AR gene in prostate cancer risk in Macedonian males. A total of 392 male subjects, 134 PC patients, 106 patients with benign prostatic hyperplasia (BPH) and 152 males from the general Macedonian population were enrolled in this study. The CAG repeat length was determined by fluorescent polymerase chain reaction (PCR) amplification of exon1 of the AR gene followed by capillary electrophoresis (CE) on a genetic analyzer. The mean repeat length in PC patients was 21.5 ±2.65, in controls 22.28 ±2.86 (p = 0.009) and in BPH patients 22.1 ±2.52 (p = 0.038). Short CAG repeats (<19) were found in 21.64% of PC patients vs. 9.43% in BPH patients (p = 0.0154). We also found an association of low Gleason score (<7) with short CAG repeat (<19) in PC patients (p = 0.0306), and no association between the age at diagnosis of PC and BPH and CAG repeat length. These results suggest that reduced CAG repeat length may be associated with increased prostate cancer risk in Macedonian men.

CAG Repeat Polymorphism in the Androgen Receptor Gene in Women with Rheumatoid Arthritis

2011 ◽  
Vol 39 (1) ◽  
pp. 10-17 ◽  
Author(s):  
VIOLETTA DZIEDZIEJKO ◽  
MATEUSZ KURZAWSKI ◽  
KRZYSZTOF SAFRANOW ◽  
ANDRZEJ OSSOWSKI ◽  
JAROSLAW PIATEK ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Androgen Receptor ◽  
White Women ◽  
Receptor Gene ◽  
Study Groups ◽  
Androgen Receptor Gene ◽  
Cag Repeat ◽  
Cag Repeats ◽  
Repeat Polymorphism ◽  
Erosive Disease

Objective.Rheumatoid arthritis (RA) is the most common chronic, autoimmune, inflammatory disease, with a genetic and hormonal background. The prevalence of women among patients with RA suggests the important role of sex hormones in the pathogenesis of RA. We examined the association between CAG repeat polymorphism in the androgen receptor (AR) gene and susceptibility to RA and its clinical features in white women.Methods.The study groups consisted of 325 female patients with RA and 238 female controls. CAG repeat polymorphism was determined using polymerase chain reaction and subsequent fragment analysis by capillary electrophoresis.Results.The number of CAG repeats in patients did not differ from that of controls (22.1 ± 2.9 vs 21.9 ± 2.9, respectively; p = 0.26), but the presence of articular erosions was associated with a lower number of repeats in the shorter allele of patients with RA (20.4 ± 2.2 vs 21.2 ± 2.4; p = 0.031). When alleles with < 22 CAG were classified as short (S) and those with ≥ 22 CAG as long (L), the age at diagnosis of RA was lower in women with S-S genotype in comparison to combined S-L + L-L genotypes (43.0 ± 14.6 yrs vs 47.6 ± 12.5 yrs; p = 0.021). In patients with the L-L genotype, the frequency of erosive disease (OR 0.45, 95% CI 0.25–0.80, p = 0.0085) and extraarticular manifestations (OR 0.50, 95% CI 0.26–0.98, p = 0.047) was lower in comparison to carriers of the S allele. In multivariate analysis, the L-L genotype was an independent factor associated with a lower risk of erosions (OR 0.44, 95% CI 0.22–0.90, p = 0.024).Conclusion.The results suggest the association of short AR (CAG)n alleles with earlier onset and a more aggressive course of RA.

The Impact of Androgen Receptor CAG Repeat Polymorphism on Andropausal Symptoms in Different Serum Testosterone Levels

2012 ◽  
Vol 9 (9) ◽  
pp. 2429-2437 ◽  
Author(s):  
Chia‐Chu Liu ◽  
Yung‐Chin Lee ◽  
Chii‐Jye Wang ◽  
Hsin‐Chih Yeh ◽  
Wei‐Ming Li ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Serum Testosterone ◽  
Cag Repeat ◽  
Repeat Polymorphism ◽  
Testosterone Levels ◽  
The Impact

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 Small effect of the androgen receptor gene GGN repeat polymorphism on serum testosterone levels in healthy men

2009 ◽  
Vol 161 (1) ◽  
pp. 171-177 ◽  
Author(s):  
Veerle Bogaert ◽  
Griet Vanbillemont ◽  
Youri Taes ◽  
Dirk De Bacquer ◽  
Ellen Deschepper ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Receptor Gene ◽  
Serum Testosterone ◽  
Cag Repeat ◽  
Repeat Polymorphism ◽  
Significant Positive Association ◽  
Cross Sectional ◽  
Healthy Men ◽  
Testosterone Levels ◽  
Androgen Action

ObjectiveThe human androgen receptor (AR) contains a polyglutamine and a polyglycine stretch which are highly polymorphic and are coded respectively by a CAG and GGN repeat in exon 1 of the AR gene. Although the in vitro studies indicated a possible effect of the GGN repeat polymorphism on the AR gene transcription and clinical observations suggest that it might modulate the androgen action, its functional significance remains unclear. We wanted to assess whether the GGN repeat affects the serum testosterone levels in healthy men, which is the expected outcome through feedback regulation if it influences androgen action as has been shown to be the case for the CAG repeat.Design and patientsA population based cross-sectional cohort study including 1476 healthy young, middle-aged, and elderly men.MeasurementTestosterone and LH levels were determined by immunoassay; free testosterone (FT) levels were calculated. Genotyping of the GGN repeat was performed using the sequencing technique.ResultsThe GGN repeat number was significantly associated with circulating testosterone and FT levels (P=0.017 and P=0.013 respectively). However, taking into account that age, body mass index, and CAG are already in the regression model, the GGN repeat could explain only a small part of the variation of both testosterone and FT.ConclusionTo our knowledge, this study is the first to demonstrate a significant positive association between the GGN repeat and androgen levels in a large cohort of healthy men. Although the present study thus adds credence to the view that the polyglycine tract in the AR can modulate AR action, this effect appears to be only small so that its clinical relevance remains questionable.

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