A novel sequence variation in the transactivation regulating domain of the androgen receptor in two infertile Finnish men.

OBJECTIVE: To study a new sequence variant at the beginning of the CAG repeat in the exon 1 of the androgen receptor gene. DESIGN: Controlled clinical study. SETTINGS: Healthy volunteers in an academic research environment. PATIENT(S): Sixty-two Finnish men with spermatogenic failure and 60 controls. INTERVENTION(S): ABI PRISM 377 (Applied Biosystems, Foster City, CA) automated sequencing. MAIN OUTCOME MEASURE(S): Determining the sequence around the CAG repeat of the AR gene. RESULT(S): A new 173A-->T (Q58L) substitution at the beginning of the CAG repeat in the transactivation-regulating domain of the androgen receptor was found in 2 infertile Finnish men but not in 60 other infertile men or 60 controls. CONCLUSION(S): As the polyglutamine tract coded by the CAG repeat is crucial to spermatogenesis, the 173A-->T (Q58L) substitution might be the cause of infertility in these two Finnish men.

Long CAG repeats in the AR gene are not associated with infertility in Finnish males.

BACKGROUND: The modulatory domain of the human androgen receptor gene contains a polymorphic CAG repeat coding for a polyglutamine tract. The length of the polyglutamine tract is inversely correlated with transcriptional activity of the androgen receptor. As androgens are crucial to spermatogenesis, decreased transcriptional activity of the androgen receptor associated with a long polyglutamine tract could lead to failure in spermatogenesis. Accordingly, long CAG repeats within the normal range have been suggested to be more common in infertile males than in the control population. METHODS: To test this hypothesis, we examined the CAG repeat number of 192 Finnish males with moderate or severe spermatogenic failure and 149 control males. RESULTS: Our results did not support the hypothesis, the controls harbored slightly longer CAG repeats than the infertile males. CONCLUSION: At least in the present study population from Finland, long CAG repeats in the androgen receptor gene do not play a significant role in spermatogenic failure.