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 (CAG) tract of the androgen receptor gene are associated with spermatogenic defects in patients with male infertility.


METHODS
Case-control study of two ethnic groups.


METHODS
University referral centers for male infertility at Baylor College of Medicine, Houston, Texas, and National University Hospital, Singapore.


METHODS
Two hundred and fifteen patients with male infertility and depressed spermatogenesis and 142 fertile controls.


METHODS
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 examination of its relation to clinical variables.


RESULTS
In U.S. patients, the mean androgen receptor CAG length was significantly longer in infertile patients than in fertile controls (21.95 +/- 0.31 vs. 20.72 +/- 0.52). Logistic regression showed that each unit increase in CAG length was associated with a 20% increase in the odds of being azoospermic. The odds ratio for azoospermia was sevenfold higher for patients with > or =26 CAG repeats than in those with <26 CAG repeats. Although mean CAG length in Singapore patients was longer than in the U.S. samples, long androgen receptor CAG alleles were significantly related to male infertility in both populations.


CONCLUSIONS
Long (> or =26) androgen receptor CAG alleles, which are found in up to 25% of azoospermic men, are associated with male infertility and defective spermatogenesis. Conception in these men is possible with assisted reproductive technologies, as many have spermatozoa in their testes.
Mifsud
A
A
Department of Obstetrics and Gynecology, National University Hospital of Singapore, Level 2, Lower Kent Ridge Road, Republic of Singapore.
Sim
C K
CK
Boettger-Tong
H
H
Moreira
S
S
Lamb
D J
DJ
Lipshultz
L I
LI
Yong
E L
EL
D001706:Biopsy; D016022:Case-Control Studies; D003062:Codon; D005006:Ethnicity / Q000235:genetics; D005819:Genetic Markers; D006801:Humans; D007248:Infertility, Male / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D009845:Oligospermia / Q000235:genetics; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011944:Receptors, Androgen / Q000235:genetics*; D012307:Risk Factors; D012846:Singapore; D013091:Spermatogenesis; D013737:Testis / Q000473:pathology; D018911:Trinucleotide Repeats; D014481:United States
D003062:Codon; D005819:Genetic Markers; D011944:Receptors, Androgen