This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hickey, T. Articles by Norman, R. J. Search for Related Content PubMed PubMed Citation Articles by Hickey, T. Articles by Norman, R. J.

The Androgen Receptor CAG Repeat Polymorphism and X-Chromosome Inactivation in Australian Caucasian Women with Infertility Related to Polycystic Ovary Syndrome

Reproductive Medicine Unit, Department of Obstetrics and Gynecology, University of Adelaide, The Queen Elizabeth Hospital, Woodville SA 5011, Australia

Address all correspondence and requests for reprints to: Theresa Hickey, M.D., Adelaide University, Department of Obstetrica and Gynecology, The Queen Elizabeth Hospital, First Floor, Maternity Building, 28 Woodville Road, Woodville, SA 5011, Australia. E-mail: theresa.hickey{at}adelaide.edu.au

The human androgen receptor (AR) gene contains a polymorphic trinucleotide (CAG) repeat sequence in exon 1. The number of CAG repeats may confer differential receptor activity, and specific ranges of variants have been correlated with androgen-sensitive disease processes. Polycystic ovary syndrome (PCOS) is a female condition characterized by androgen excess and infertility, many features of which are effected through the AR. We compared frequency distributions of CAG repeat alleles and their pattern of expression via X-inactivation analysis among 83 fertile women and 122 infertile women with PCOS, all of Australian Caucasian ethnicity. A population comparison with 831 predominantly fertile Australian women was also used. PCR-based assays were used to genotype each woman and assess allele inactivation patterns after digestion of DNA with methylation-sensitive HpaII. Infertile women with PCOS exhibited a greater frequency of CAG alleles or biallelic means greater than 22 repeats compared with both the fertile control group (P < 0.05) and the general population (P < 0.01). Preferential expression of longer CAG repeat alleles was also observed in PCOS and correlated with increased serum T. We conclude that the AR (CAG)n gene locus and/or its differential methylation patterns influence the disease process leading to PCOS.

Abbreviations: AR, Androgen receptor; hAR, human AR; PCOS, polycystic ovary syndrome.

This article has been cited by other articles:

				M. Simoni, C.B. Tempfer, B. Destenaves, and B.C.J.M. Fauser Functional genetic polymorphisms and female reproductive disorders: Part I: polycystic ovary syndrome and ovarian response Hum. Reprod. Update, July 4, 2008; (2008) dmn024v1. [Abstract] [Full Text] [PDF]

				N. A. Shah, H. J. Antoine, M. Pall, K. D. Taylor, R. Azziz, and M. O. Goodarzi Association of Androgen Receptor CAG Repeat Polymorphism and Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., May 1, 2008; 93(5): 1939 - 1945. [Abstract] [Full Text] [PDF]

				M.O. Goodarzi, N. Xu, J. Cui, X. Guo, Y.I. Chen, and R. Azziz Small glutamine-rich tetratricopeptide repeat-containing protein alpha (SGTA), a candidate gene for polycystic ovary syndrome Hum. Reprod., May 1, 2008; 23(5): 1214 - 1219. [Abstract] [Full Text] [PDF]

				S. Lappalainen, P. Utriainen, T. Kuulasmaa, R. Voutilainen, and J. Jaaskelainen Androgen Receptor Gene CAG Repeat Polymorphism and X-Chromosome Inactivation in Children with Premature Adrenarche J. Clin. Endocrinol. Metab., April 1, 2008; 93(4): 1304 - 1309. [Abstract] [Full Text] [PDF]

				N. Xita, I. Georgiou, L. Lazaros, V. Psofaki, G Kolios, and A. Tsatsoulis The role of sex hormone-binding globulin and androgen receptor gene variants in the development of polycystic ovary syndrome Hum. Reprod., March 1, 2008; 23(3): 693 - 698. [Abstract] [Full Text] [PDF]

				K.A. Walters, C.M. Allan, and D.J. Handelsman Androgen Actions and the Ovary Biol Reprod, March 1, 2008; 78(3): 380 - 389. [Abstract] [Full Text] [PDF]

				K. K Ong, F. de Zegher, A. Lopez-Bermejo, D. B Dunger, and L. Ibanez Flutamide metformin for post-menarcheal girls with preclinical ovarian androgen excess: evidence for differential response by androgen receptor genotype Eur. J. Endocrinol., November 1, 2007; 157(5): 661 - 668. [Abstract] [Full Text] [PDF]

				K. A. Walters, C. M. Allan, M. Jimenez, P. R. Lim, R. A. Davey, J. D. Zajac, P. Illingworth, and D. J. Handelsman Female Mice Haploinsufficient for an Inactivated Androgen Receptor (AR) Exhibit Age-Dependent Defects That Resemble the AR Null Phenotype of Dysfunctional Late Follicle Development, Ovulation, and Fertility Endocrinology, August 1, 2007; 148(8): 3674 - 3684. [Abstract] [Full Text] [PDF]

				S. Rajender, V. Rajani, N. J. Gupta, B. Chakravarty, L. Singh, and K. Thangaraj No Association of Androgen Receptor GGN Repeat Length Polymorphism With Infertility in Indian Men J Androl, November 1, 2006; 27(6): 785 - 789. [Abstract] [Full Text] [PDF]

				C. Hughes, M. Elgasim, R. Layfield, and W. Atiomo Genomic and post-genomic approaches to polycystic ovary syndrome--progress so far: Mini Review Hum. Reprod., November 1, 2006; 21(11): 2766 - 2775. [Abstract] [Full Text] [PDF]

				M. Mohlig, A. Jurgens, J. Spranger, K. Hoffmann, M. O Weickert, H. W Schlosser, T. Schill, G. Brabant, A. Schuring, A. F H Pfeiffer, et al. The androgen receptor CAG repeat modifies the impact of testosterone on insulin resistance in women with polycystic ovary syndrome. Eur. J. Endocrinol., July 1, 2006; 155(1): 127 - 130. [Abstract] [Full Text] [PDF]

				T. E. Hickey, R. S. Legro, and R. J. Norman Epigenetic Modification of the X Chromosome Influences Susceptibility to Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., July 1, 2006; 91(7): 2789 - 2791. [Abstract] [Full Text] [PDF]

				D.H. Abbott, D.K. Barnett, C.M. Bruns, and D.A. Dumesic Androgen excess fetal programming of female reproduction: a developmental aetiology for polycystic ovary syndrome? Hum. Reprod. Update, July 1, 2005; 11(4): 357 - 374. [Abstract] [Full Text] [PDF]

				H. F. Escobar-Morreale, M. Luque-Ramirez, and J. L. San Millan The Molecular-Genetic Basis of Functional Hyperandrogenism and the Polycystic Ovary Syndrome Endocr. Rev., April 1, 2005; 26(2): 251 - 282. [Abstract] [Full Text] [PDF]

				D. A. Ehrmann Polycystic Ovary Syndrome N. Engl. J. Med., March 24, 2005; 352(12): 1223 - 1236. [Full Text] [PDF]

				I. S. Brum, P. M. Spritzer, F. Paris, M. A. Maturana, F. Audran, and C. Sultan Association Between Androgen Receptor Gene CAG Repeat Polymorphism and Plasma Testosterone Levels in Postmenopausal Women Reproductive Sciences, February 1, 2005; 12(2): 135 - 141. [Abstract] [PDF]

				M. Zitzmann, M. Depenbusch, J. Gromoll, and E. Nieschlag X-Chromosome Inactivation Patterns and Androgen Receptor Functionality Influence Phenotype and Social Characteristics as Well as Pharmacogenetics of Testosterone Therapy in Klinefelter Patients J. Clin. Endocrinol. Metab., December 1, 2004; 89(12): 6208 - 6217. [Abstract] [Full Text] [PDF]

				D. Lattuada, P. Vigano, E. Somigliana, M. P. Odorizzi, M. Vignali, and A. M. Di Blasio Androgen Receptor Gene Cytosine, Adenine, and Guanine Trinucleotide Repeats in Patients With Endometriosis Reproductive Sciences, May 1, 2004; 11(4): 237 - 240. [Abstract] [PDF]

				L Pinson, J Auge, S Audollent, G Mattei, H Etchevers, N Gigarel, F Razavi, D Lacombe, S Odent, M Le Merrer, et al. Embryonic expression of the human MID1 gene and its mutations in Opitz syndrome J. Med. Genet., May 1, 2004; 41(5): 381 - 386. [Full Text] [PDF]

				L. Ibanez, K. K. Ong, N. Mongan, J. Jaaskelainen, M. V. Marcos, I. A. Hughes, F. de Zegher, and D. B. Dunger Androgen Receptor Gene CAG Repeat Polymorphism in the Development of Ovarian Hyperandrogenism J. Clin. Endocrinol. Metab., July 1, 2003; 88(7): 3333 - 3338. [Abstract] [Full Text] [PDF]

				S. Dejager, H. Bry-Gauillard, E. Bruckert, B. Eymard, F. Salachas, E. LeGuern, S. Tardieu, R. Chadarevian, P. Giral, and G. Turpin A Comprehensive Endocrine Description of Kennedy's Disease Revealing Androgen Insensitivity Linked to CAG Repeat Length J. Clin. Endocrinol. Metab., August 1, 2002; 87(8): 3893 - 3901. [Abstract] [Full Text] [PDF]

				S. B. Seminara and W. F. Crowley Jr. Genetic Approaches to Unraveling Reproductive Disorders: Examples of Bedside to Bench Research in the Genomic Era Endocr. Rev., June 1, 2002; 23(3): 382 - 392. [Abstract] [Full Text] [PDF]