Association of AR rs6152G/A gene polymorphism with susceptibility to polycystic ovary syndrome in Chinese women
C. Y. Peng A B C , X. Y. Long A B and G. X. Lu A B D
+ Author Affiliations
- Author Affiliations
A Institute of Human Reproduction and Stem Cell Engineering, Central South University, 110 Xiangya Road, Changsha, Hunan, China.
B Reproductive and Genetic Hospital of CITIC-XIANGYA, 110 Xiangya Road, Changsha, Hunan, China.
C Present address: Department of Pharmacy and Life Science, University of South China, Hengyang 421001, China.
D Corresponding author. Email: lugxdirector@yahoo.com.cn
Reproduction, Fertility and Development 22(5) 881-885 https://doi.org/10.1071/RD09190
Submitted: 13 August 2009 Accepted: 10 December 2009 Published: 15 April 2010
Abstract
Hyperandrogenism is a central feature of polycystic ovary syndrome (PCOS). Androgens act via the androgen receptor (AR). The rs6152G/A AR gene polymorphism has been reported to be associated with male pattern baldness (MPB), which is a common characteristic of males in PCOS families. Therefore, we investigated the relationship between the rs6152G/A polymorphism and PCOS in Han Chinese women. The rs6152G/A AR gene polymorphism was screened by restriction fragment length polymorphism (RFLP) in 224 PCOS women and 223 control subjects from the Reproductive and Genetic Hospital of CITIC-XIANGYA in China. There was a significantly higher prevalence of genotypes containing the A allele in PCOS patients compared with controls (P < 0.05). Patients carrying the rs6152A allele had a 1.608-fold greater risk of developing polycystic ovary syndrome compared with rs6152GG homozygotes (OR = 1.608, CI = 1.008–2.597, P < 0.05). In conclusion, the individuals carrying the rs6152A allele had significantly higher susceptibility to polycystic ovary syndrome than those that were GG homozygotes.
Additional keyword: androgen receptor.
Acknowledgements
This work was partially supported by grants from the no. 973 National Research Program of China (2007CB948103) and the National Basic Research Program of China (00CB51010). The authors are indebted to K. Li of Suzhou University for valuable advice and sincere assistance with the manuscript.
References
Asunción, M. , Calvo, R. M. , San Millán, J. L. , Sancho, J. , Avila, S. , and Escobar-Morreale, H. F. (2000). A prospective study of the prevalence of the polycystic ovary syndrome in unselected Caucasian women from Spain. J. Clin. Endocrinol. Metab. 85, 2434–2438.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Braillon, A. (2005). Polycystic ovary syndrome. N. Engl. J. Med. 352, 2756–2757.
| Crossref | GoogleScholarGoogle Scholar | PubMed | CAS |
Buchanan, G. , Yang, M. , Harris, J. M. , Nahm, H. S. , and Han, G. , et al. (2001). Mutations at the boundary of the hinge and ligand-binding domain of the androgen receptor confer increased transactivation function. Mol. Endocrinol. 15, 46–56.
| Crossref | GoogleScholarGoogle Scholar | PubMed | CAS |
Buchanan, G. , Yang, M. , Cheong, A. , Harris, J. M. , and Irvine, R. A. , et al. (2004). Structural and functional consequences of glutamine tract variation in the androgen receptor. Hum. Mol. Genet. 13, 1677–1692.
| Crossref | GoogleScholarGoogle Scholar | PubMed | CAS |
Carey, A. H. , Chan, K. L. , Short, F. , White, D. , Williamson, R. , and Franks, S. (1993). Evidence for a single gene effect causing polycystic ovaries and male pattern baldness. Clin. Endocrinol. (Oxf.) 38, 653–658.
| Crossref | GoogleScholarGoogle Scholar | PubMed | CAS |
Carey, A. H. , Waterworth, D. , Patel, K. , White, D. , Little, J. , Novelli, P. , Franks, S. , and Williamson, R. (1994). Polycystic ovaries and premature male pattern baldness are associated with one allele of the steroid metabolism gene CYP17. Hum. Mol. Genet. 3, 1873–1876.
| Crossref | GoogleScholarGoogle Scholar | PubMed | CAS |
Cooper, H. E. , Spellacy, W. N. , Prem, K. A. , and Cohen, W. D. (1968). Hereditary factors in the Stein–Leventhal syndrome. Am. J. Obstet. Gynecol. 100, 371–387.
| PubMed | CAS |
Cude, K. J. , Montgomery, J. S. , Price, D. K. , Dixon, S. C. , and Kincaid, R. L. , et al. (2002). The role of an androgen receptor polymorphism in the clinical outcome of patients with metastatic prostate cancer. Urol. Int. 68, 16–23.
| Crossref | GoogleScholarGoogle Scholar | PubMed | CAS |
Dumesic, D. A. , Schramm, R. D. , and Abbott, D. H. (2005). Early origins of polycystic ovary syndrome. Reprod. Fertil. Dev. 17, 349–360.
| Crossref | GoogleScholarGoogle Scholar | PubMed | CAS |
Dunaif, A. (1997). Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. Endocr. Rev. 18, 774–800.
| Crossref | GoogleScholarGoogle Scholar | PubMed | CAS |
Ehrmann, D. A. (2005). Polycystic ovary syndrome. N. Engl. J. Med. 352, 1223–1236.
| Crossref | GoogleScholarGoogle Scholar | PubMed | CAS |
Ellis, J. A. , Stebbing, M. , and Harrap, S. B. (2001). Polymorphism of the androgen receptor gene is associated with male pattern baldness. J. Invest. Dermatol. 116, 452–455.
| Crossref | GoogleScholarGoogle Scholar | PubMed | CAS |
Ellis, J. A. , Scurrah, K. J. , Cobb, J. E. , Zaloumis, S. G. , Duncan, A. E. , and Harrap, S. B. (2007). Baldness and the androgen receptor: the AR polyglycine repeat polymorphism does not confer susceptibility to androgenetic alopecia. Hum. Genet. 121, 451–457.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Ferlin, A. , Vinanzi, C. , Garolla, A. , Selice, R. , Zuccarello, D. , Cazzadore, C. , and Foresta, C. (2006). Male infertility and androgen receptor gene mutations: clinical features and identification of seven novel mutations. Clin. Endocrinol. (Oxf.) 65, 606–610.
| Crossref | GoogleScholarGoogle Scholar | PubMed | CAS |
Ferriman, D. , and Purdie, A. W. (1979). The inheritance of polycystic ovarian disease and a possible relationship to premature balding. Clin. Endocrinol. (Oxf.) 11, 291–300.
| Crossref | GoogleScholarGoogle Scholar | PubMed | CAS |
Franks, S. (1989). Polycystic ovary syndrome: a changing perspective. Clin. Endocrinol. (Oxf.) 31, 87–120.
| Crossref | GoogleScholarGoogle Scholar | PubMed | CAS |
Franks, S. (1991). The ubiquitous polycystic ovary. J. Endocrinol. 129, 317–319.
| Crossref | GoogleScholarGoogle Scholar | PubMed | CAS |
Franks, S. (1995). Polycystic ovary syndrome. N. Engl. J. Med. 333, 853–861.
| Crossref | GoogleScholarGoogle Scholar | PubMed | CAS |
Givens, J. R. (1988). Familial polycystic ovarian disease. Endocrinol. Metab. Clin. North Am. 17, 771–783.
| PubMed | CAS |
Goldzieher, J. W. , and Green, J. A. (1962). The polycystic ovary. I. Clinical and histologic features. J. Clin. Endocrinol. Metab. 22, 325–338.
| Crossref | GoogleScholarGoogle Scholar | PubMed | CAS |
Greenland, K. J. , Beilin, J. , Castro, J. , Varghese, P. N. , and Zajac, J. D. (2004). Polymorphic CAG repeat length in the androgen receptor gene and association with neurodegeneration in a heterozygous female carrier of Kennedy’s disease. J. Neurol. 251, 35–41.
| Crossref | GoogleScholarGoogle Scholar | PubMed | CAS |
Hague, W. M. , Adams, J. , Reeders, S. T. , Peto, T. E. , and Jacobs, H. S. (1988). Familial polycystic ovaries: a genetic disease? Clin. Endocrinol. (Oxf.) 29, 593–605.
| Crossref | GoogleScholarGoogle Scholar | PubMed | CAS |
Hickey, T. , Chandy, A. , and Norman, R. J. (2002). The androgen receptor CAG repeat polymorphism and X-chromosome inactivation in Australian Caucasian women with infertility related to polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 87, 161–165.
| Crossref | GoogleScholarGoogle Scholar | PubMed | CAS |
Hillmer, A. M. , Brockschmidt, F. F. , Hanneken, S. , Eigelshoven, S. , and Steffens, M. , et al. (2008). Susceptibility variants for male-pattern baldness on chromosome 20p11. Nat. Genet. 40, 1279–1281.
| Crossref | GoogleScholarGoogle Scholar | PubMed | CAS |
Hiort, O. , Huang, Q. , Sinnecker, G. H. , Sadeghi-Nejad, A. , Kruse, K. , Wolfe, H. J. , and Yandell, D. W. (1993). Single strand conformation polymorphism analysis of androgen receptor gene mutations in patients with androgen insensitivity syndromes: application for diagnosis, genetic counselling, and therapy. J. Clin. Endocrinol. Metab. 77, 262–266.
| Crossref | GoogleScholarGoogle Scholar | PubMed | CAS |
Jääskeläinen, J. , Korhonen, S. , Voutilainen, R. , Hippeläinen, M. , and Heinonen, S. (2005). Androgen receptor gene CAG length polymorphism in women with polycystic ovary syndrome. Fertil. Steril. 83, 1724–1728.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Kim, J. J. , Choung, S. H. , Choi, Y. M. , Yoon, S. H. , Kim, S. H. , and Moon, S. Y. (2008). Androgen receptor gene CAG repeat polymorphism in women with polycystic ovary syndrome. Fertil. Steril. 90, 2318–2323.
| Crossref | GoogleScholarGoogle Scholar | PubMed | CAS |
Knochenhauer, E. S. , Key, T. J. , Kahsar-Miller, M. , Waggoner, W. , Boots, L. R. , and Azziz, R. (1998). Prevalence of the polycystic ovary syndrome in unselected black and white women of the south-eastern United States: a prospective study. J. Clin. Endocrinol. Metab. 83, 3078–3082.
| Crossref | GoogleScholarGoogle Scholar | PubMed | CAS |
Kunkel, L. M. , Smith, K. D. , Boyer, S. H. , Borgaonkar, D. S. , Wachtel, S. S. , Miller, O. J. , Breg, W. R. , Jones, H. W. , and Rary, J. M. (1977). Analysis of human Y-chromosome-specific reiterated DNA in chromosome variants. Proc. Natl. Acad. Sci. USA 74, 1245–1249.
| Crossref | GoogleScholarGoogle Scholar | PubMed | CAS |
Marszalek, B. , Lacinski, M. , Babych, N. , Capla, E. , Biernacka-Lukanty, J. , Warenik-Szymankiewicz, A. , and Trzeciak, W. H. (2001). Investigations on the genetic polymorphism in the region of CYP17 gene encoding 5′-UTR in patients with polycystic ovarian syndrome. Gynecol. Endocrinol. 15, 123–128.
| PubMed | CAS |
McEwan, I. J. (2001). Structural and functional alterations in the androgen receptor in spinal bulbar muscular atrophy. Biochem. Soc. Trans. 29, 222–227.
| Crossref | GoogleScholarGoogle Scholar | PubMed | CAS |
Mifsud, A. , Ramirez, S. , and Yong, E. L. (2000). Androgen receptor gene CAG trinucleotide repeats in anovulatory infertility and polycystic ovaries. J. Clin. Endocrinol. Metab. 85, 3484–3488.
| Crossref | GoogleScholarGoogle Scholar | PubMed | CAS |
Möhlig, M. , Jürgens, A. , Spranger, J. , Hoffmann, K. , and Weickert, M. O. , et al. (2006). The androgen receptor CAG repeat modifies the impact of testosterone on insulin resistance in women with polycystic ovary syndrome. Eur. J. Endocrinol. 155, 127–130.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Rojanasakul, A. , Gustavson, K. H. , Lithell, H. , and Nillius, S. J. (1985). Tetraploidy in two sisters with the polycystic ovary syndrome. Clin. Genet. 27, 167–174.
| PubMed | CAS |
Rosenfield, R. L. (1999). Ovarian and adrenal function in polycystic ovary syndrome. Endocrinol. Metab. Clin. North Am. 28, 265–293.
| Crossref | GoogleScholarGoogle Scholar | PubMed | CAS |
Rotterdam, ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group (2004a). Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil. Steril. 81, 19–25.
| Crossref | GoogleScholarGoogle Scholar |
Rotterdam, ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group (2004b). Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum. Reprod. 19, 41–47.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Shah, N. A. , Antoine, H. J. , Pall, M. , Taylor, K. D. , Azziz, R. , and Goodarzi, M. O. (2008). Association of androgen receptor CAG repeat polymorphism and polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 93, 1939–1945.
| Crossref | GoogleScholarGoogle Scholar | PubMed | CAS |
Xita, N. , Georgiou, I. , Lazaros, L. , Psofaki, V. , Kolios, G. , and Tsatsoulis, A. (2008). The role of sex hormone-binding globulin and androgen receptor gene variants in the development of polycystic ovary syndrome. Hum. Reprod. 23, 693–698.
| Crossref | GoogleScholarGoogle Scholar | PubMed | CAS |
Yildiz, B. O. , Yarali, H. , Oguz, H. , and Bayraktar, M. (2003). Glucose intolerance, insulin resistance, and hyperandrogenemia in first-degree relatives of women with polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 88, 2031–2036.
| Crossref | GoogleScholarGoogle Scholar | PubMed | CAS |
