Trinucleotide (CAG) repeat polymorphisms in the androgen receptor gene: Molecular markers of risk for male infertility
Open accessAbstract
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.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 examination of its relation to clinical variables.Result(s) 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.Conclusion(s) 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.
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Studies of CAG repeats and hypogonadal symptoms found findings similar to those in men with low testosterone, including depressed mood, anxiety, impaired spermatogenesis, and loss of bone mineral density.
“Results demonstrated findings similar to those observed in men with low T, including depressed mood, anxiety, impaired spermatogenesis, and loss of bone mineral density (BMD), among others.”
From Challenges in Testosterone Measurement, Data Interpretation, and Methodological Appraisal of Interventional Trials (2016) · cites this paper as [31]
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- Authors
- Mifsud, A., Sim, C. K. S., Boettger-Tong, H., Moreira, S., Lamb, D. J., Lipshultz, L. I., & Yong, E. L.
- Affiliations
- National University of Singapore (SG)
- Baylor College of Medicine (US)
- Venue
- Fertility and Sterility
- Publisher
- Elsevier BV
- Published
- 2001-02
- Volume
- 75
- Issue
- 2
- Pages
- 275-281
- ISSN
- 0015-0282 (ISSN-L)
- OpenAlex
- W2042606922
- Cited by
- 139
- References
- 30
- Citations by year
- 2024: 2 · 2023: 1 · 2022: 1 · 2021: 4 · 2020: 2 · 2019: 1 · 2018: 1 · 2017: 1 · 2016: 5 · 2015: 4 · 2014: 3 · 2013: 6 · 2012: 7
- FWCI
- 15.30
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Fertility and Sterility (publishedVersion)
- PubMed (publishedVersion)
- National University of Singapore (submittedVersion)
- Funders
- National Institutes of Health
- Medical Research Council
- National Medical Research Council
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P01HD036289)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Keywords
- androgen receptor gene, CAG repeat polymorphism, trinucleotide repeat expansion, male infertility, azoospermia, spermatogenesis defects, genetic risk markers
- MeSH terms
- Biopsy, Codon, Ethnicity, Genetic Markers, Humans, Infertility, Male, Male, Oligospermia, Polymorphism, Genetic, Receptors, Androgen, Risk Factors, Singapore, Spermatogenesis, Testis, United States, Logistic Models, Case-Control Studies, Polymerase Chain Reaction, Trinucleotide Repeats
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