O-91: Association of long polyglutamine tracts in exon 1 of the androgen receptor gene with idiopathic male infertility and impaired sperm production in Iranian population

Abstract

To determine whether changes in the polyglutamine tracts in exon 1 of the androgen receptor gene are associated with idiopathic male infertility and impaired sperm production in Iranian population. Case-control study of association the polymorphic trinucleotide (CAG) in the androgen receptor gene with idiopathic male infertility. We performed a case-control study of 178 Iranian males with idiopathic infertility witch were excluded for androgen receptor mutations and Y chromosome microdeletions and 152 fertile males as control. The length of the CAG repeat segment was evaluated by using PCR-sequencing in exon 1 and PCR-SSCP in exons 2-8. We were able to identify 13 different alleles in the infertile group with a range of 18-32 CAG repeats corresponding to 19-33 glutamine residues. The mean of the AR gene CAG repeat length in the infertile group was 24.13 ± 1.64 (range 18-32), while that of fertile controls was 20.32 ± 0.92 (range 16-25) and the difference was statistically significant (P = 0.001). The highest mean length of the AR gene CAG number in infertile group was observed in oligospermia group (24.21) but there were not significant differences between the Oligospermia and Azoospermia. In addition, the frequency of having a CAG repeat number (≥ 21) was 79% in infertile men and 27.1% in fertile controls (P = 0.001), whereas the of having a CAG repeat number (≥ 26) was 23.6% in infertile males versus 0% in fertile controls. In the same infertile patient group the most common allele in azoospermic group consisted of 23 CAG repeats (27.7%; 24 glutamine residues respectively) and in oligospermic group consisted of 24 CAG repeats (23.1%; 25 glutamine residues respectively). The most common alleles in the fertile control group consisted of 20 CAG repeats (25.1%) corresponding to 21 glutamine residues respectively. No mutation was detected in exons 2-8 of androgen receptor gene in infertile patients. Long (≥26) androgen receptor CAG alleles, which are found in up to 38% of infertile males, are associated with male infertility and defective spermatogenesis and the odds ratio for male infertility was higher for patients with ≥26 CAG repeat than in those with <26 CAG repeats.