Androgen receptor polymorphism (CAG repeats) and androgenicity

Objective: Cryptorchidism is the most common congenital birth defect in male children, and accumulating evidence suggests that genetic abnormalities may be associated with it. The androgen receptor has two polymorphic sites in exon 1, with different numbers of CAG and GGC repeats, resulting in variable lengths of polyglutamine and polyglycine stretches. Longer CAG repeats result in a reduced androgen receptor transcriptional activity, but the role of the GGC triplets is less clear. In this study we analysed CAG and GGC repeat lengths in men with a history of cryptorchidism, associated or not with impairment of sperm production, in comparison with normal fertile subjects. Methods: We analysed CAG and GGC repeat lengths in a group of 105 ex-cryptorchid men in comparison with 115 fertile non-cryptorchid men. Results: No difference was found between patients and controls in the mean and median values, and in distribution of CAG and GGC, when considered separately. However, the analysis of the joint distribution of CAG and GGC showed that some combinations are significantly more frequent in men with bilateral cryptorchidism (who frequently presented severe testiculopathies), in a manner similar to that found in idiopathic infertile subjects. Conclusions: Although further studies are needed to elucidate the possible role of specific CAG/GGC combinations as a causative factor, these data suggest a possible association between androgen receptor gene polymorphisms and cryptorchidism.

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

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.86.6.7614 ◽

2001 ◽

Vol 86 (6) ◽

pp. 2562-2568 ◽

Cited By ~ 3

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.

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