Abstract
Context: Genetically determined heightened androgen sensitivity may influence the phenotype of polycystic ovary syndrome (PCOS). To date, studies of the androgen receptor exon 1 polymorphic CAG repeat have produced conflicting results in PCOS. Objective: We tested the hypothesis that a lower number of CAG repeats is associated with increased odds of PCOS. We also compared X-chromosome inactivation between cases and controls. Design: Women with and without PCOS were genotyped for the CAG repeat and assessed for X-chromosome methylation. Association analyses were performed. Setting: Subjects were recruited from the reproductive endocrinology clinic at the University of Alabama at Birmingham; controls were recruited from the surrounding community. Genotyping took place at Cedars-Sinai Medical Center in Los Angeles. Participants: Participants included 330 women with PCOS and 289 controls (77% white, 23% black). Main Measurements: Androgen receptor genotype, X-chromosome methylation, and phenotyping for PCOS were measured. Results: A smaller biallelic mean of CAG repeats was associated with increased odds of PCOS. X-chromosome inactivation was not different comparing cases with controls; however, in the subset with nonrandom inactivation, the chromosome bearing the shorter CAG allele was preferentially active in PCOS women. Conclusions: Association of shorter CAG repeats with PCOS is consistent with in vitro functional studies demonstrating higher activity of androgen receptors expressed from alleles with fewer CAG repeats, suggesting inherited alteration in androgen sensitivity may contribute to PCOS. In some women, such heightened sensitivity may also result from preferential expression of androgen receptors with shorter alleles. Thus, genetic and epigenetic changes may be involved in the pathogenesis of PCOS.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1939-1945 |
| Number of pages | 7 |
| Journal | Journal of Clinical Endocrinology and Metabolism |
| Volume | 93 |
| Issue number | 5 |
| DOIs | |
| State | Published - May 2008 |
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ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Biochemistry
- Endocrinology
- Clinical Biochemistry
- Biochemistry, medical
Cite this
Association of androgen receptor CAG repeat polymorphism and polycystic ovary syndrome. / Shah, Nissar A.; Antoine, Heath J.; Pall, Marita; Taylor, Kent D.; Azziz, Ricardo; Goodarzi, Mark O.
In: Journal of Clinical Endocrinology and Metabolism, Vol. 93, No. 5, 05.2008, p. 1939-1945.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Association of androgen receptor CAG repeat polymorphism and polycystic ovary syndrome
AU - Shah, Nissar A.
AU - Antoine, Heath J.
AU - Pall, Marita
AU - Taylor, Kent D.
AU - Azziz, Ricardo
AU - Goodarzi, Mark O.
PY - 2008/5
Y1 - 2008/5
N2 - Context: Genetically determined heightened androgen sensitivity may influence the phenotype of polycystic ovary syndrome (PCOS). To date, studies of the androgen receptor exon 1 polymorphic CAG repeat have produced conflicting results in PCOS. Objective: We tested the hypothesis that a lower number of CAG repeats is associated with increased odds of PCOS. We also compared X-chromosome inactivation between cases and controls. Design: Women with and without PCOS were genotyped for the CAG repeat and assessed for X-chromosome methylation. Association analyses were performed. Setting: Subjects were recruited from the reproductive endocrinology clinic at the University of Alabama at Birmingham; controls were recruited from the surrounding community. Genotyping took place at Cedars-Sinai Medical Center in Los Angeles. Participants: Participants included 330 women with PCOS and 289 controls (77% white, 23% black). Main Measurements: Androgen receptor genotype, X-chromosome methylation, and phenotyping for PCOS were measured. Results: A smaller biallelic mean of CAG repeats was associated with increased odds of PCOS. X-chromosome inactivation was not different comparing cases with controls; however, in the subset with nonrandom inactivation, the chromosome bearing the shorter CAG allele was preferentially active in PCOS women. Conclusions: Association of shorter CAG repeats with PCOS is consistent with in vitro functional studies demonstrating higher activity of androgen receptors expressed from alleles with fewer CAG repeats, suggesting inherited alteration in androgen sensitivity may contribute to PCOS. In some women, such heightened sensitivity may also result from preferential expression of androgen receptors with shorter alleles. Thus, genetic and epigenetic changes may be involved in the pathogenesis of PCOS.
AB - Context: Genetically determined heightened androgen sensitivity may influence the phenotype of polycystic ovary syndrome (PCOS). To date, studies of the androgen receptor exon 1 polymorphic CAG repeat have produced conflicting results in PCOS. Objective: We tested the hypothesis that a lower number of CAG repeats is associated with increased odds of PCOS. We also compared X-chromosome inactivation between cases and controls. Design: Women with and without PCOS were genotyped for the CAG repeat and assessed for X-chromosome methylation. Association analyses were performed. Setting: Subjects were recruited from the reproductive endocrinology clinic at the University of Alabama at Birmingham; controls were recruited from the surrounding community. Genotyping took place at Cedars-Sinai Medical Center in Los Angeles. Participants: Participants included 330 women with PCOS and 289 controls (77% white, 23% black). Main Measurements: Androgen receptor genotype, X-chromosome methylation, and phenotyping for PCOS were measured. Results: A smaller biallelic mean of CAG repeats was associated with increased odds of PCOS. X-chromosome inactivation was not different comparing cases with controls; however, in the subset with nonrandom inactivation, the chromosome bearing the shorter CAG allele was preferentially active in PCOS women. Conclusions: Association of shorter CAG repeats with PCOS is consistent with in vitro functional studies demonstrating higher activity of androgen receptors expressed from alleles with fewer CAG repeats, suggesting inherited alteration in androgen sensitivity may contribute to PCOS. In some women, such heightened sensitivity may also result from preferential expression of androgen receptors with shorter alleles. Thus, genetic and epigenetic changes may be involved in the pathogenesis of PCOS.
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UR - http://www.scopus.com/inward/citedby.url?scp=43249126965&partnerID=8YFLogxK
U2 - 10.1210/jc.2008-0038
DO - 10.1210/jc.2008-0038
M3 - Article
C2 - 18303071
AN - SCOPUS:43249126965
VL - 93
SP - 1939
EP - 1945
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 5
ER -