Influence of CAG Repeat Polymorphism on the Targets of Testosterone Action

Abstract

In the last decade, ample evidence has demonstrated the growing importance of androgen receptor (AR) CAG repeat polymorphism in andrology. This genetic parameter is able to condition the peripheral effects of testosterone and therefore to influence male sexual function and fertility, cardiovascular risk, body composition, bone metabolism, the risk of prostate and testicular cancer, the psychiatric status, and the onset of neurodegenerative disorders. In this review, we extensively discuss the literature data and identify a role for AR CAG repeat polymorphism in conditioning the systemic testosterone effects. In particular, our main purpose was to provide an updated text able to shed light on the many and often contradictory findings reporting an influence of CAG repeat polymorphism on the targets of testosterone action.

Endothelial function in men with type 2 diabetes without clinical signs of cardiovascular disease

“…Так, исследования последних лет показали важную роль андрогенного дефицита у мужчин в развитии сердечно-сосудистых заболеваний и ЭД [15,16]. Установлено, что геномные эффекты тестостерона обусловлены по-лиморфизмом гена рецептора андрогенов [17]. Учитывая взаимосвязь полиморфизма гена рецептора андрогенов и ЭД [18], вызывает интерес определение его влияния на время наступления максимальной вазодилятации, что дает предпосылки для проведения новых исследо-ваний.…”

Androgen receptor (AR) gene (CAG)n and (GGN)n length polymorphisms and symptoms in young males with long-lasting adverse effects after finasteride use against androgenic alopecia

“…17 Long (CAG) n repeats have been associated with decreased AR transactivation activity and weaker transcriptional potential than short repeats. 18 CAG expanded repeats of at least 40 have been found in Kennedy disease, a neurodegenerative syndrome also characterized by androgen insensitivity.…”

“…17,18,21 In contrast, a meta-analysis suggested that a shorter (CAG)n repeat polymorphism in Caucasians and Asians might increase the risk of prostate cancer compared with the longer (CAG)n repeat.…”

Androgen receptor GGC repeat might be more involved than CAG repeat in the regulation of the metabolic profile in men

“…The polymorphic sequence of the CAG repeat usually varies in number from 10 to 35, and encodes polyglutamine stretches of AR transactivation domain [10,11]. The majority of the findings suggest that the CAG number is negatively correlated to the transcriptional activity of AR, and as a result, to the effects of testosterone [10,12,13].…”

“…The majority of the findings suggest that the CAG number is negatively correlated to the transcriptional activity of AR, and as a result, to the effects of testosterone [10,12,13]. This relationship has also been evaluated in regard to the metabolic effect.…”