Negative association between androgen receptor gene CAG repeat polymorphism and polycystic ovary syndrome? A systematic review and meta-analysis

Molecular Human Reproduction

Volumn 18, Issue 10, 2012, Pages 498-509

  Wang, Rui ^a   Goodarzi, Mark O ^b   Xiong, Ting ^a   Wang, Di ^a   Azziz, Ricardo ^c   Zhang, Hanwang ^a  

^a HUAZHONG UNIVERSITY OF SCIENCE AND TECHNOLOGY   (China)

^b CEDARS SINAI MEDICAL CENTER   (United States)

^c MEDICAL COLLEGE OF GEORGIA   (United States)

Author keywords

Androgen receptor; CAG repeat; Genetic polymorphism; Meta analysis; Polycystic ovary syndrome

Indexed keywords

ANDROGEN RECEPTOR;

ALLELE; ARTICLE; CAG REPEAT; EXON; GENETIC HETEROGENEITY; GENOTYPE; HUMAN; META ANALYSIS; OVARY POLYCYSTIC DISEASE; PRIORITY JOURNAL; SYSTEMATIC REVIEW;

ALLELES; BASE COMPOSITION; FEMALE; GENOTYPE; HUMANS; MICROSATELLITE REPEATS; POLYCYSTIC OVARY SYNDROME; POLYMORPHISM, SINGLE NUCLEOTIDE; RECEPTORS, ANDROGEN; TRINUCLEOTIDE REPEATS;

EID: 84867124904     PISSN: 13609947     EISSN: 14602407     Source Type: Journal    
DOI: 10.1093/molehr/gas024     Document Type: Article

References (46)

1. Azziz R, Carmina E, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, Futterweit W, Janssen OE, Legro RS, Norman RJ, Taylor AE et al. Positions statement: criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: an Androgen Excess Society guideline. J Clin Endocrinol Metab 2006;91:4237-4245.
2. Barber TM, Franks S. Genetic basis of polycystic ovary syndrome. Expert Rev Endocrinol Metab 2010;5:549-561.
3. Brown CJ, Goss SJ, Lubahn DB, Joseph DR, Wilson EM, French FS, Willard HF. Androgen receptor locus on the human X chromosome: regional localization to Xq11-12 and description of a DNA polymorphism. Am J Hum Genet 1989;44:264-269.
4. Buchanan G, Yang M, Cheong A, Harris JM, Irvine RA, Lambert PF, Moore NL, Raynor M, Neufing PJ, Coetzee GA et al. Structural and functional consequences of glutamine tract variation in the androgen receptor. Hum Mol Genet 2004;13:1677-1692.
5. Chamberlain NL, Driver ED, Miesfeld RL. The length and location of CAG trinucleotide repeats in the androgen receptor N-terminal domain affect transactivation function. Nucleic Acids Res 1994;22:3181-3186.
6. Chen ZJ, Zhao H, He L, Shi Y, Qin Y, Li Z, You L, Zhao J, Liu J, Liang X et al. Genome-wide association study identifies susceptibility loci for polycystic ovary syndrome on chromosome 2p16.3, 2p21 and 9q33.3. Nat Genet 2011;43:55-59.
7. Chua AK, Azziz R, Goodarzi MO. Association study of CYP17 and HSD11B1 in polycystic ovary syndrome utilizing comprehensive gene coverage. Mol Hum Reprod 2012; doi:10.1093/molehr/gas1002.
8. Dasgupta S, Sirisha PV, Neelaveni K, Anuradha K, Reddy AG, Thangaraj K, Reddy BM. Androgen receptor CAG repeat polymorphism and epigenetic influence among the south Indian women with polycystic ovary syndrome. PLoS ONE 2010;5:e12401.
9. Diaz M, Lopez-Bermejo A, Petry CJ, De Zegher F, Ibanez L. Efficacy of metformin therapy in adolescent girls with androgen excess: relation to sex hormone-binding globulin and androgen receptor polymorphisms. Fertil Steril 2010a;94:2800-2803. e2801.
10. Diaz M, Lopez-Bermejo A, Petry CJ, De Zegher F, Ibahez L. Androgen receptor gene repeat polymorphisms influence the response to metformin in adolescent girls with androgen excess. Horm Res Paediatr 2010b;74:65-66.
11. Dupont WD, Plummer WD. Power and sample size calculations: a review and computer program. Control Clin Trials 1990;11:116-128.
12. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. Br Med J 1997;315:629-634.
13. Ferk P, Perme MP, Teran N, Gersak K. Androgen receptor gene (CAG)n polymorphism in patients with polycystic ovary syndrome. Fertil Steril 2008;90:860-863.
14. Goodarzi M. Looking for polycystic ovary syndrome genes: rational and best strategy. Semin Reprod Med 2008;26:5-13.
15. Goodarzi MO, Dumesic DA, Chazenbalk G, Azziz R. Polycystic ovary syndrome: etiology, pathogenesis and diagnosis. Nat Rev Endocrinol 2011;7:219-231.
16. Hickey TE, Chandy A, Norman RJ. 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 2002;87:161-165.
17. Hickey TE, Legro RS, Norman RJ. Epigenetic modification of the X chromosome influences susceptibility to polycystic ovary syndrome. J Clin Endocrinol Metab 2006;91:2789-2791.
18. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. Br Med J 2003;327:557-560.
19. Irvine RA, Ma H, Yu MC, Ross RK, Stallcup MR, Coetzee GA. Inhibition of p160-mediated coactivation with increasing androgen receptor polyglutamine length. Hum Mol Genet 2000;9:267-274.
20. Jääskeläinen J, Korhonen S, Voutilainen R, Hippeläinen M, Heinonen S. Androgen receptor gene CAG length polymorphism in women with polycystic ovary syndrome. Fertil Steril 2005;83:1724-1728.
21. Jakubiczka S, Quaiser A, Nickel I, Kleinstein J, Wieacker P. Molecular genetic studies at the androgen receptor-gene in female patients with PCO syndrome. Geburtshilfe Frauenheilkd 1997;57:545-548.
22. Kim JJ, Choung SH, Choi YM, Yoon SH, Kim SH, Moon SY. Androgen receptor gene CAG repeat polymorphism in women with polycystic ovary syndrome. Fertil Steril 2008;90:2318-2323.
23. Laisk T, Haller-Kikkatalo K, Laanpere M, Jakovlev U, Peters M, Karro H, Salumets A. Androgen receptor epigenetic variations influence early follicular phase gonadotropin levels. Acta Obstet Gynecol Scand 2010; 89:1557-1563.
24. Lau J, Ioannidis JP, Schmid CH. Quantitative synthesis in systematic reviews. Ann Intern Med 1997;127:820-826.
25. Lin BK, Clyne M, Walsh M, Gomez O, Yu W, Gwinn M, Khoury MJ. Tracking the epidemiology of human genes in the literature: the HuGE published literature database. Am J Epidemiol 2006;164:1-4.
26. Liu Q, Hong J, Cui B, Zhang Y, Gu W, Chi Z, Su Y, Ning G. Androgen receptor gene CAG(n) trinucleotide repeats polymorphism in Chinese women with polycystic ovary syndrome. Endocrine 2008; 33:165-170.
27. McEwan IJ. Molecular mechanisms of androgen receptor-mediated gene regulation: structure-function analysis of the AF-1 domain. Endocr Relat Cancer 2004;11:281-293.
28. Mifsud A, Ramirez S, Yong EL. Androgen receptor gene CAG trinucleotide repeats in anovulatory infertility and polycystic ovaries. J Clin Endocrinol Metab 2000;85:3484-3488.
29. Mohlig M, Jurgens A, Spranger J, Hoffmann K, Weickert MO, Schlosser HW, Schill T, Brabant G, Schuring A, Pfeiffer AFH et al. The androgen receptor CAG repeat modifies the impact of testosterone on insulin resistance in women with polycystic ovary syndrome. Eur J Endocrinol 2006;155:127-130.
30. Nazarenko T, Biruykova A. Features of passing PCOS, depending on the polymorphisms of genes IRS2, AR, and PPARG. J Reproduktionsmed Endokrinol 2010;7:271.
31. Nenonen H, Bjork C, Skjaerpe PA, Giwercman A, Rylander L, Svartberg J, Giwercman YL. CAG repeat number is not inversely associated with androgen receptor activity in vitro. Mol Hum Reprod 2010;16:153-157.
32. Peng CY, Long XY, Lu GX. Association of AR rs6152G/A gene polymorphism with susceptibility to polycystic ovary syndrome in Chinese women. Reprod Fertil Dev 2010;22:881-885.
33. Radian S, Baculescu N, Aflorei D, Gussi I, Vladoiu S, Ianas O, Grigorescu F, Coculescu M. CAG repeat alleles of the androgen receptor are associated with polycystic ovary syndrome (PCOS) in the Romanian population. Endocr Abstr 2010;22:498.
34. Ramos Cirilo PD, Rosa FE, Moreira Ferraz MF, Rainho CA, Pontes A, Regina Rogatto S. Genetic polymorphisms associated with steroids metabolism and insulin action in polycystic ovary syndrome. Gynecol Endocrinol 2011. doi: 10.3109/09513590.2011.593661.
35. Robeva R, Dobreva D, Kirilov G, Mechandjiev T, Tomova A, Savov A, Kumanov F. CAG repeat polymorphism in women with PCOS and healthy controls. Endocr Abstr 2010;22:459.
36. Schüring AN, Welp A, Gromoll J, Zitzmann M, Sonntag B, Nieschlag E, Greb RR, Kiesel L. Role of the CAG Repeat Polymorphism of the Androgen Receptor Gene in Polycystic Ovary Syndrome (PCOS). Exp Clin Endocrinol Diabetes 2011. doi: 10.1055/s-0031-1291343.
37. Shah NA, Antoine HJ, Pall M, Taylor KD, Azziz R, Goodarzi MO. Association of androgen receptor CAG repeat polymorphism and polycystic ovary syndrome. J Clin Endocrinol Metab 2008;93:1939-1945.
38. Skrgatic L, Baldani DP, Cerne JZ, Ferk P, Gersak K. CAG repeat polymorphism in androgen receptor gene is not directly associated with polycystic ovary syndrome but influences serum testosterone levels. J Steroid Biochem Mol Biol 2012;128:107-112.
39. Sterne J, Michael JB, Egger M. Meta-analysis in StataTM. In: Egger M, Smith G, Altman D (eds). Systematic Reviews in Healthcare: Meta-analysis in Context, 2nd edn. London: BMJ, 2001, 347-369.
40. The Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related topolycystic ovary syndrome. Fertil Steril 2004;81:19-25.
41. Tong D, Deng J, Sun H, Chen L, Wu X. The relationship between CAG repeat length polymorphism and infertility in Southern Chinese Han women. J Endocrinol Invest 2010;33:559-563.
42. Tut TG, Ghadessy FJ, Trifiro MA, Pinsky L, Yong EL. Long polyglutamine tracts in the androgen receptor are associated with reduced trans-activation, impaired sperm production, and male infertility. J Clin Endocrinol Metab 1997;82:3777-3782.
43. Van Nieuwerburgh F, Stoop D, Cabri P, Dhont M, Deforce D, De Sutter P. Shorter CAG repeats in the androgen receptor gene may enhance hyperandrogenicity in polycystic ovary syndrome. Gynecol Endocrinol 2008;24:669-673.
44. Xita N, Georgiou I, Lazaros L, Psofaki V, Kolios G, Tsatsoulis A. The role of sex hormone-binding globulin and androgen receptor gene variants in the development of polycystic ovary syndrome. Hum Reprod 2008; 23:693-698.
45. Zawadzki JK, Dunaif A. Diagnostic criteria for polycystic ovary syndrome: towards a rational approach. In: Dunaif A, Givens J, Haseltine F, MerriamG (eds). Polycystic Ovary Syndrome. Boston: Blackwell, 1992, 377-384.
46. Zeegers MP, Kiemeney LALM, Nieder AM, Ostrer H. How strong is the association between CAG and GGN repeat length polymorphisms in the androgen receptor gene and prostate cancer risk? Cancer Epidemiol Biomark Prev 2004;13:1765-1771.