Androgen receptor polymorphism (CAG repeats) and androgenicity

Abstract

Summary Objective Polymorphism of the androgen receptor (AR) has been related to various pathophysiological conditions, such as osteoporosis and infertility. The objectives of this study were to evaluate the frequency of distribution in a normal Italian population and to assess CAG repeats (CAGr) in other conditions, such as hypoandrogenism, potentially influenced by AR polymorphism. Patients and measurements CAGr polymorphism was determined in a group of 91 healthy normoandrogenized subjects, 29 hypoandrogenized patients (hypoplasia of prostate and seminal vesicles, reduced beard or body hair, etc.) and 29 infertile patients by direct sequencing. Results The mean (± SD) number of CAG repeats [(CAGr)n] was 21·5 (± 1·7) in the control group, 21·4 (± 2·0) in the infertile patients and 24·0 (± 2·9) in the hypoandrogenic males. The difference was statistically significant between this last group and the other two (P < 0·0001), while there was no difference between normal controls and infertile patients. The frequency distribution showed a shift towards higher CAG length in hypoandrogenized patients compared to controls and infertile patients. If we used a cut‐off point of 24·9 (2 SD above the mean), the percentage of patients with 25 or more CAGr repeats was 38% among hypoandrogenized patients, 7% among infertile patients and 5% among the control group. In hypoandrogenized subjects (CAGr)n correlated slightly with testis and prostate volume. The number of CAG repeats was not associated with any of the hormonal parameters, including testosterone, evaluated in the three groups. Conclusions Our normal population, representing subjects from Central Italy, is superimposable on other European populations with regard to (CAGr)n distribution. Hypoandrogenic males have a shift in the frequency distribution towards longer (CAGr)n. Infertile patients are not statistically different from the control group. These findings suggest that, given the same amount of circulating testosterone, as in our hypoandrogenized and control group, the final net androgenic phenotypical effect is due to AR polymorphism.

Spatial abilities are not related to testosterone levels and variation in the androgen receptor in healthy young men

“…Apparent discrepancies between studies may be underlined by differences in population genetic background, and the age of enrolled men. There is one study in young men, which did not find significant association between testosterone levels and a number of CAG repeats (Canale et al 2005). These and our results suggest that the current testosterone levels are independent of androgen receptor sensitivity.…”

Could androgen receptor gene CAG tract polymorphism affect spermatogenesis in men with idiopathic infertility?

“…1), indicating that trinucleotide CAG repeat length might co-regulate the AR function, being different the distribution both between fertile and infertile male and even between the well-known forms of infertility and the idiopathic ones. These data can gain more weight if one considers that the range of our fertile participants was not different form those reported by other Italian Authors in previously published works [40][41][42]. Indeed, in a paper by Canale et al [42] the Authors showed a range of 18-26 CAG repeats with only one case with CAG repeat number >25 in the control group, while in another paper by Ferlin et al [41], the control group had a wide range of 9-30, event though the patients with CAG repeat number below 15 were only 3 % and those above 25 were less than 10 %.…”

“…These data can gain more weight if one considers that the range of our fertile participants was not different form those reported by other Italian Authors in previously published works [40][41][42]. Indeed, in a paper by Canale et al [42] the Authors showed a range of 18-26 CAG repeats with only one case with CAG repeat number >25 in the control group, while in another paper by Ferlin et al [41], the control group had a wide range of 9-30, event though the patients with CAG repeat number below 15 were only 3 % and those above 25 were less than 10 %. Finally, delli Muti et al [40] showed a range of 15-27 with only 3 % of subjects with trinucleotide CAG repeat number above 25 in their control group.…”

The androgen receptor and prostate cancer: A role for sexual selection and sexual conflict?

“…There is also an inverse correlation between CAG repeat length and androgenicity (e.g. [35]). Decreased repeat length is associated with increased production of prostate specific antigen and increased sperm count in adolescent males [36,37].…”