Analysis of the CAG repeat number in exon 1 of the androgen receptor gene in Slovene men with idiopathic azoospermia and oligoasthenoteratozoospermia

I am Borut Peterlin, from Division of Medical Genetics, Department of Obstetrics and Gynaecology, University Medical Center, Ljubljana, Slovenia. We write to you to discuss if the number of CAG repeats in the androgen receptor (AR) gene is associated with male infertility in a group of 190 Slovene infertile men compared to 137 men with proven fertility. Pathophysiology of subfertility involves a complex network of genetic and environmental factors. Stimulation and maintenance of spermatogenesis require androgens and functional AR. The first exon of the AR gene contains a polymorphic CAG repeat coding for a polyglutamine tract. Expansion of the CAG repeats to 40 or more causes spinal and bulbar muscular atrophy (SBMA) [1]. Besides progressive muscle weakness and atrophy, patients also show signs of mild androgen insensitivity: endocrine disturbances (including gynaecomastia), testicular atrophy, oligozoospermia, azoospermia, impairment of sperm quality and infertility. Both in vivo and in vitro studies have demonstrated reduced transactivation potential of the AR as the polyglutamine tract increased in length [2]. Inverse correlation between sperm concentration and the number of androgen receptor CAG repeats was found within the normal fertile population; shorter CAG repeats were associated with higher sperm output [3]. The concept of the potential pathogenic effect of longer CAG repeats in the range of 24–40 (CAG)n is important not only for better understanding of the etiology of male infertility, but also for the treatment of infertile men. Ten studies to date have shown the existence of the correlation between CAG repeat number and male infertility (in Chinese, Japanese, North American, French, Israeli, Taiwan [China] and Spanish populations), but 20 other studies did not confirm the association (in Swedish, Belgian, German, Japanese, Danish, Dutch, Indian, Greek, New Zealander, Finish, Hong Kong [China] and Italian populations) [4]. No data are available for Slavic populations. In this letter, we would like to provide such data gained from a group of 190 Slovene infertile men compared to 137 men with proven fertility. Patients with obstructive azoospermia as a result of epididymal stenosis or congenital bilateral absence of deferens and those with Klinefelter and Kallman syndrome, cytogenetic abnormalities and Y chromosome microdeletions were excluded. The study group con-