scholarly journals Lack of Influence of the Androgen Receptor Gene CAG-Repeat Polymorphism on Clinical and Electrocardiographic Manifestations of the Brugada Syndrome in Man

2012 ◽  
Vol 6 ◽  
pp. CMC.S10553 ◽  
Author(s):  
S. Mariani ◽  
B. Musumeci ◽  
S. Basciani ◽  
D. Fiore ◽  
P. Francia ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Brugada Syndrome ◽  
Clinical Manifestations ◽  
Cag Repeat ◽  
Cag Repeats ◽  
Sex Hormone Binding Globulin ◽  
Blood Levels ◽  
Repeat Polymorphism ◽  
Male Predominance ◽  
Increased Risk

Background Clinical studies suggest that testosterone (T) plays an important role in the male predominance of the clinical manifestations of the Brugada syndrome (BS). However, no statistically significant correlations have been observed between T levels and electrocardiogram (ECG) parameters in the BS patients. We investigated whether the hormonal pattern and the variation within CAG repeat polymorphism in exon 1 of the androgen receptor (AR) gene, affecting androgen sensitivity, are associated with the Brugada ECG phenotype in males. Methods and Results 16 male patients with BS (mean age 45.06 ± 11.3 years) were studied. 12-lead ECG was recorded. Blood levels of follicle-stimulating hormone, luteinizing hormone, prolactin, testosterone, free-T, dihydrotestosterone, 17-β-estradiol, estrone, 3-alpha-androstanediol-glucuronide, delta-4-androstenedione, dehydroepiandrosterone sulphate, progesterone, 17-hydroxyprogesterone, and sex hormone binding globulin were assayed. Genotyping of CAG repeats on DNA extracted from leukocytes was carried out. No relationship was found between hormone values and ECG parameters of BS. BS patients showed the CAG length normally recognized in the human polymorphism range and the number of CAG repeats did not correlate with the ECG pattern of BS. Conclusions The AR CAG repeat length does not correlate with the ECG features of the patients affected by BS. The search for genes downstream AR activation as possibly responsible for the increased risk of spontaneous arrhythmias in BS males after puberty is warranted.

scholarly journals The CAG Repeat Polymorphism in the Androgen Receptor Gene Is Associated with HDL-Cholesterol but Not with Coronary Atherosclerosis or Myocardial Infarction

2005 ◽  
Vol 51 (7) ◽  
pp. 1110-1115 ◽  
Author(s):  
Martin Hersberger ◽  
Jörg Muntwyler ◽  
Harald Funke ◽  
Jacqueline Marti-Jaun ◽  
Helmut Schulte ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Androgen Receptor ◽  
Confidence Interval ◽  
Odds Ratio ◽  
Target Genes ◽  
Hdl Cholesterol ◽  
Cag Repeat ◽  
Cag Repeats ◽  
Repeat Polymorphism ◽  
Increased Risk

Abstract Background: Age-adjusted morbidity and mortality rates from coronary heart disease (CHD) are higher in men than in women. Androgens are suspected to be responsible for the male disadvantage. The genomic effect of androgens is mediated by the androgen receptor (AR), which has a polymorphic CAG repeat in exon 1. The number of repeats is inversely related to the transcriptional activity of the AR on target genes. Methods: We investigated the association of this CAG repeat polymorphism with CHD and myocardial infarction (MI) in 2 independent case–control studies involving 544 Caucasian men. Results: The number of CAG repeats in the AR gene correlated significantly with HDL-cholesterol (HDL-C) in controls (r = 0.21; P = 0.015). This effect was independent of triglycerides, body mass index, alcohol intake, smoking, and age in a multiple regression model (R2 = 50%). Despite decreased HDL-C, lower CAG repeat numbers were not associated with increased risk for CHD (odds ratio = 0.82; 95% confidence interval, 0.50–1.36; P = 0.44) or MI in carriers of AR genes with lower CAG repeat numbers (odds ratio = 0.72; 95% confidence interval, 0.37–1.39; P = 0.33). Conclusions: Shorter, more androgenic AR alleles with fewer CAG repeats are associated with lower HDL-C, but not with an increased risk for CHD or MI, which argues against a detrimental androgen effect on cardiovascular risk under physiologic conditions.

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.

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.

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.

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 Impact of constitutional genetic variation in androgen/oestrogen-regulating genes on age-related changes in human prostate

2002 ◽  
pp. 479-484 ◽  
Author(s):  
AR Azzouzi ◽  
B Cochand-Priollet ◽  
P Mangin ◽  
G Fournier ◽  
P Berthon ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Receptor Gene ◽  
Cag Repeat ◽  
Cag Repeats ◽  
Dna Polymorphisms ◽  
Prostate Hyperplasia ◽  
Hormone Synthesis ◽  
Age Related ◽  
Increased Risk ◽  
Prostate Enlargement

OBJECTIVE: Benign prostatic hyperplasia (BPH) is the most common benign tumour in ageing men. While the etiopathology remains unsolved, a disruption in the endocrine/autocrine-paracrine prostatic homeostasis, involving steroid hormones, contributes to the pathogenesis of BPH. DNA polymorphisms in genes involved in hormone synthesis, signalling and metabolism may, therefore, be responsible for these changes. We have evaluated the correlation between specific genotypes in androgen- and oestrogen-regulating genes (AR, SRD5A2, CYP17 and CYP19), and age-related prostatic changes. METHODS: We have tested genetic susceptibility to morphological and pathological criteria in 195 French Caucasians, using allelic variants for candidate genes involved in androgen/oestrogen prostatic activity: androgen receptor (CAG repeats), 5alpha-reductase type 2 (TA repeats, V89L and A49T mutations), A2 variant of the 17alpha-hydroxylase (CYP17) and the simple tandem repeat polymorphism (STRP) aromatase (CYP19) polymorphisms. RESULTS: The A2 variant of 17alpha-hydroxylase (CYP17) and allele 191 of STRP aromatase (CYP19) showed an opposite effect on age-related prostate hyperplasia: CYP17 being associated with increased risk of prostate enlargement and CYP19 with reduced risk. The 5alpha-reductase type II variants studied did not show links with prostate hyperplasia. The androgen receptor gene CAG repeat length showed a low correlation with the increase of prostate weight, suggesting some effect on age-related prostate growth. CONCLUSION: These results suggested that common variants of the CYP17 gene are associated with prostate enlargement and therefore may increase the risk of development of BPH in this population, while infrequent variants of the aromatase gene (CYP19) could be of a protective nature.

scholarly journals Evidence that the CAG repeat in the androgen receptor gene is associated with the age-related decline in serum androgen levels in men

1999 ◽  
Vol 162 (1) ◽  
pp. 137-142 ◽  
Author(s):  
K Krithivas ◽  
SM Yurgalevitch ◽  
BA Mohr ◽  
CJ Wilcox ◽  
SJ Batter ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Repeat Length ◽  
Cag Repeat ◽  
Cag Repeats ◽  
Sex Hormone Binding Globulin ◽  
Sample Survey ◽  
Hormone Levels ◽  
Age Related ◽  
Androgen Levels

In men over 30 years old, serum levels of testosterone (T) decrease with age. A shorter polymorphic CAG repeat length in exon 1 of the androgen receptor (AR) gene is associated with higher transcription activation by the AR. We determined the number of CAG repeats for 882 men aged between 40 and 70 years from the Massachusetts Male Aging Study (MMAS). MMAS is a population-based random sample survey of men for whom baseline (1987-1989, mean age 53+/-8 years) and follow-up (1995-1997, mean age 61+/-8 years) serum hormone levels were available. Multiple linear regression was used to determine if CAG repeat length would be predictive of hormone levels at follow-up. Hormone levels measured included T, free T, albumin-bound T, dihydrotestosterone (DHT), sex hormone-binding globulin (SHBG) and luteinizing hormone (LH). The CAG repeat length was significantly associated with T (P=0.041), albumin-bound T (P=0.025) and free T (P=0.003) when controlled for age, baseline hormone levels and anthropometrics. Follow-up levels of T decreased by 0.74%+/-0.36 per CAG repeat decrement. Likewise, the percentages of free and albumin-bound T decreased by 0.93%+/-0.31 and 0.71%+/-0.32 per CAG repeat decrement respectively. These results suggest that androgen levels may be modulated by AR genotype.

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