Trinucleotide (CAG) repeat polymorphisms in the androgen receptor gene: molecular markers of risk for male infertility

Objective: To determine whether changes in the polymorphic trinucleotide (C AG) tract of the androgen receptor gene are associated with spermatogenic d efects in patients with male infertility. Design: Case-control study of two ethnic groups. Setting: University referral centers for male infertility at Baylor College of Medicine, Houston, Texas, and National University Hospital. Singapore. Participant(s): Two hundred and fifteen patients with male infertility and depressed spermatogenesis and 142 fertile controls. Main Outcome Measure(s): Size of androgen receptor CAG alleles according to fluorescent-labeled polymerase chain reaction and automated analysis using Genescan software (PE Biosystems Asia, Singapore), and statistical examina tion of its relation to clinical variables. Result(s): In U.S. patients, the mean androgen receptor CAG length was sign ificantly longer in infertile patients than in fertile controls (21.95 +/- 0.31 vs. 20.72 +/- 0.52), Logistic regression showed that each unit increas e in CAG length was associated with a 20% increase in the odds of being azo ospermic. The odds ratio for azoospermia was sevenfold higher for patients with greater than or equal to 26 CAG repeats than in those with < 26 CAG re peats. Although mean CAG length in Singapore patients was longer than in th e U.S. samples, long androgen receptor CAG alleles were significantly relat ed to male infertility in both populations. Conclusion(s): Long (<greater than or equal to> 26) androgen receptor CAG a lleles, which are found in up to 25% of azoospermic men, are associated wit h male infertility and defective spermatogenesis. Conception in these men i s possible with assisted reproductive technologies. as many have spermatozo a in their testes. (C) 2001 by American Society for Reproductive Medicine.