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Mol. Hum. Reprod. Advance Access originally published online on March 25, 2004
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Molecular Human Reproduction, Vol. 10, No. 6, pp. 417-421, 2004
© European Society of Human Reproduction and Embryology 2004

Androgen receptor gene CAG and GGC repeat lengths in idiopathic male infertility

A. Ferlin1, L. Bartoloni1, G. Rizzo1, A. Roverato2, A. Garolla1 and C. Foresta1,3

1University of Padova, Department of Medical and Surgical Sciences, Centre for Male Gamete Cryopreservation, Padova and 2University of Modena and Reggio Emilia, Department of Social, Cognitive and Quantitative Sciences, Modena, Italy

3 To whom correspondence should be addressed at: University of Padova, Department of Medical and Surgical Sciences, Centre for Male Gamete Cryopreservation, Via Ospedale 105, 35128 Padova, Italy. e-mail carlo.foresta{at}unipd.it

The androgen receptor (AR) has two polymorphic sites in exon 1, characterized by different numbers of CAG and GGC repeats resulting in variable lengths of polyglutamine and polyglycine stretches. Longer CAG repeats result in a reduced AR transcriptional activity, whereas the role of the GGC triplets is less clear. A relationship between decreased spermatogenesis and moderate expansion in the CAG tract has been found in some studies, but not in others. Furthermore, the joint distribution of CAG and GGC repeats in male infertility has never been reported before. We analysed CAG and GGC repeat lengths in a group of 163 men with idiopathic infertility compared with 115 fertile normozoospermic men. 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 the distribution of particular haplotypes is significantly different between patients and controls. In particular, two CAG/GGC haplotypes seem to increase susceptibility to infertility (CAG = 21/GGC = 18 and CAG ≥21/GGC ≥18, relative risk 2.47 and 1.6), while one haplotype (CAG ≥23/GGC ≤16, relative risk 0.09) seems to confer a protective effect against the disease. These data show a combined effect of CAG and GGC repeat numbers on AR function and the first evidence of a relationship of particular CAG/GGC haplotypes with male infertility.

Key words: androgen receptor/CAG/GGC/male infertility/triplets


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