Fertility and Sterility
Volume 90, Issue 5 , Pages 2010.e9-2010.e12 , November 2008

Evidence for association of the G1733A polymorphism of the androgen receptor gene with recurrent spontaneous abortions

  • Maria Karvela, B.Sc.

      Affiliations

    • Division of Genetics and Biotechnology, Department of Biology, University of Athens, Athens, Greece
    • ,
  • Nikolaos Stefanakis, B.Sc.

      Affiliations

    • Division of Genetics and Biotechnology, Department of Biology, University of Athens, Athens, Greece
    • ,
  • Sophia Papadopoulou, B.Sc.

      Affiliations

    • Division of Genetics and Biotechnology, Department of Biology, University of Athens, Athens, Greece
    • ,
  • Sonia G. Tsitilou, Ph.D.

      Affiliations

    • Division of Biochemistry and Molecular Biology, Department of Biology, University of Athens, Athens, Greece
    • ,
  • Vasileios Tsilivakos, M.D.

      Affiliations

    • Department of Infertility, Locus Medicus Laboratory, Athens, Greece
    • ,
  • Klea Lamnissou, Ph.D.

      Affiliations

    • Division of Genetics and Biotechnology, Department of Biology, University of Athens, Athens, Greece
    • Corresponding Author InformationReprint requests: Klea Lamnissou, Ph.D., Division of Genetics and Biotechnology, Department of Biology, University of Athens, Panepistimioupolis, Ano Ilisia, Athens 15701, Greece (FAX: 30-210-7274318).

Received 31 January 2008 ,Revised 23 April 2008 ,Accepted 30 April 2008.

References 

  1. Wilcox AJ, Weinberg CR, O'Connor JF, Baird DD, Schlatterer JP, Canfield RE, et al. Incidence of early loss of pregnancy. N Engl J Med. 1988;319:189–194
  2. Tempfer C, Unfried G, Zeillinger R, Hefler L, Nagele F, Huber JC. Endothelial nitric oxide synthase gene polymorphism in women with idiopathic recurrent miscarriage. Hum Reprod. 2001;16:1644–1647
  3. Yoshimura T, Yoshimura M, Tabata A, Yasue H, Okamura H. The missense Glu298Asp variant of the endothelial nitric oxide synthase gene is strongly associated with placental abruption. Hum Genet. 2001;108:181–183
  4. Hefler LA, Tempfer CB, Bashford MT, Unfried G, Zeillinger R, Schneeberger C, et al. Polymorphisms of the angiotensinogen gene, the endothelial nitric oxide synthase gene, and the interleukin-1beta gene promoter in women with idiopathic recurrent miscarriage. Mol Hum Reprod. 2002;8:95–100
  5. Buchholz T, Lohse P, Kosian E, Thaler CJ. Vasoconstrictively acting AT1R A1166C and NOS3 4/5 polymorphisms in recurrent spontaneous abortions (RSA). Am J Reprod Immunol. 2004;51:323–328
  6. Papazoglou D, Galazios G, Papatheodorou K, Liberis V, Papanas N, Maltezos E, et al. Vascular endothelial growth factor gene polymorphisms and idiopathic recurrent pregnancy loss. Fertil Steril. 2005;83:959–963
  7. Zammiti W, Mtiraoui N, Mercier E, Abboud N, Saidi S, Mahjoub T, et al. Association of factor V gene polymorphisms (Leiden; Cambridge; Hong Kong and HR2 haplotype) with recurrent idiopathic pregnancy loss in Tunisia. A case-control study. Thromb Haemost. 2006;95:612–617
  8. Karvela M, Papadopoulou S, Tsaliki E, Hatzaki A, Florentin-Arar L, Lamnissou K. Endothelial nitric oxide synthase gene polymorphisms in recurrent spontaneous abortions. Arch Gynecol Obstet. In press.
  9. Quigley CA, De Bellis A, Marschke KB, el-Awady MK, Wilson EM, French FS. Androgen receptor defects: historical, clinical, and molecular perspectives. Endocr Rev. 1995;16:271–321
  10. Brown CJ, Goss SJ, Lubahn DB, Joseph DR, Wilson EM, French FS, et al. 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
  11. 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
  12. Ding D, Xu L, Menon M, Reddy GP, Barrack ER. Effect of GGC (glycine) repeat length polymorphism in the human androgen receptor on androgen action. Prostate. 2005;62:133–139
  13. Lu J, Danielsen M. A Stu I polymorphism in the human androgen receptor gene (AR). Clin Genet. 1996;49:323–324
  14. Grad JM, Lyons LS, Robins DM, Burnstein KL. The androgen receptor (AR) amino-terminus imposes androgen-specific regulation of AR gene expression via an exonic enhancer. Endocrinology. 2001;142:1107–1116
  15. Ross RK, Pike MC, Coetzee GA, Reichardt JK, Yu MC, Feigelson H, et al. Androgen metabolism and prostate cancer: establishing a model of genetic susceptibility. Cancer Res. 1998;58:4497–4504
  16. Medeiros R, Vasconcelos A, Costa S, Pinto D, Morais A, Oliveira J, et al. Steroid hormone genotypes ARSTuI and ER325 are linked to the progression of human prostate cancer. Cancer Genet Cytogenet. 2003;141:91–96
  17. Giovannucci E, Stampfer MJ, Krithivas K, Brown M, Dahl D, Brufsky A, et al. The CAG repeat within the androgen receptor gene and its relationship to prostate cancer. Proc Natl Acad Sci U S A. 1997;94:3320–3323
  18. 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. In press.
  19. Acromite MT, Mantzoros CS, Leach RE, Hurwitz J, Dorey LG. Androgens in preeclampsia. Am J Obstet Gynecol. 1999;180:60–63
  20. Carlsen SM, Romundstad P, Jacobsen G. Early second-trimester maternal hyperandrogenemia and subsequent preeclampsia: a prospective study. Acta Obstet Gynecol Scand. 2005;84:117–121
  21. Saarela T, Jääskeläinen J, Tenhola S, Voutilainen R, Heinonen S. Preeclampsia and androgen receptor gene CAG repeat length: results from both children and women. J Assist Reprod Genet. 2005;22:269–275
  22. Bachmann J, Feldmer M, Ganten U, Stock G, Ganten D. Sexual dimorphism of blood pressure: possible role of the renin-angiotensin system. J Steroid Biochem Mol Biol. 1991;40:511–515
  23. Mantzoros CS, Georgiadis EI, Young R, Evagelopoulou C, Khoury S, Katsilambros N, et al. Relative androgenicity, blood pressure levels, and cardiovascular risk factors in young healthy women. Am J Hypertens. 1995;8:606–614
  24. Gustafson DR, Wen MJ, Koppanati BM. Androgen receptor gene repeats and indices of obesity in older adults. Int J Obes Relat Metab Disord. 2003;27:75–81
  25. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988;16:1215
  26. Unfried G, Tempfer C, Schneeberger C, Widmar B, Nagele F, Huber JC. Interleukin 1 receptor antagonist polymorphism in women with idiopathic recurrent miscarriage. Fertil Steril. 2001;75:683–687
  27. Montgomery JS, Price DK, Figg WD. The androgen receptor gene and its influence on the development and progression of prostate cancer. J Pathol. 2001;195:138–146
  28. Giovannucci E, Stampfer MJ, Chan A, Krithivas K, Gann PH, Hennekens CH, et al. CAG repeat within the androgen receptor gene and incidence of surgery for benign prostatic hyperplasia in U.S. physicians. Prostate. 1999;39:130–134
  29. Roberts RO, Jacobson DJ, Rhodes T, Klee GG, Leiber MM, Jacobsen SJ. Serum sex hormones and measures of benign prostatic hyperplasia. Prostate. 2004;61:124–131
  30. Ochsenkühn R, De Kretser DM. The contributions of deficient androgen action in spermatogenic disorders. Int J Androl. 2003;26:195–201
  31. Davis-Dao CA, Tuazon ED, Sokol RZ, Cortessis VK. Male infertility and variation in CAG repeat length in the androgen receptor gene: a meta-analysis. J Clin Endocrinol Metab. 2007;92:4319–4326
  32. Terry KL, De Vivo I, Titus-Ernstoff L, Shih MC, Cramer DW. Androgen receptor cytosine, adenine, guanine repeats, and haplotypes in relation to ovarian cancer risk. Cancer Res. 2005;65:5974–5981
  33. McGrath M, Lee IM, Hankinson SE, Kraft P, Hunter DJ, Buring J, et al. Androgen receptor polymorphisms and endometrial cancer risk. Int J Cancer. 2006;118:1261–1268
  34. Langdahl BL, Stenkjaer L, Carstens M, Tofteng CL, Eriksen EF. A CAG repeat polymorphism in the androgen receptor gene is associated with reduced bone mass and increased risk of osteoporotic fractures. Calcif Tissue Int. 2003;73:237–243
  35. Elhaji YA, Gottlieb B, Lumbroso R, Beitel LK, Foulkes WD, Pinsky L, et al. The polymorphic CAG repeat of the androgen receptor gene: a potential role in breast cancer in women over 40. Breast Cancer Res Treat. 2001;70:109–116
  36. Giguère Y, Dewailly E, Brisson J, Ayotte P, Laflamme N, Demers A, et al. Short polyglutamine tracts in the androgen receptor are protective against breast cancer in the general population. Cancer Res. 2001;61:5869–5874
  37. Cox DG, Blanché H, Pearce CL, Calle EE, Colditz GA, Pike MC, et al. A comprehensive analysis of the androgen receptor gene and risk of breast cancer: results from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3). Breast Cancer Res. 2006;8:R54
  38. Weihua Z, Ekman J, Almkvist A, Saji S, Wang L, Gustafsson JA, et al. Involvement of androgen receptor in 17beta-estradiol-induced cell proliferation in rat uterus. Biol Reprod. 2002;67:616–623
  39. Shiina H, Matsumoto T, Sato T, Igarashi K, Miyamoto J, Takemasa S, et al. Premature ovarian failure in androgen receptor-deficient mice. Proc Natl Acad Sci U S A. 2006;103:224–229
  40. Walters KA, Allan CM, Jimenez M, Lim PR, Davey RA, Zajac JD, et al. 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. 2007;148:3674–3684
  41. Esteban E, Via M, González-Pérez E, Santamaría J, Dugoujon JM, Vona G, et al. An unexpected wide population variation of the G1733A polymorphism of the androgen receptor gene: data on the Mediterranean region. Am J Hum Biol. 2005;17:690–695
  42. Ribeiro ML, Santos A, Carvalho-Salles AB, Hackel C. Allelic frequencies of six polymorphic markers for risk of prostate cancer. Braz J Med Biol Res. 2002;35:205–213

 M.K. has nothing to disclose. N.S. has nothing to disclose. S.P. has nothing to disclose. S.G.T. has nothing to disclose. V.T. has nothing to disclose. K.L. has nothing to disclose.

 Supported by the Special Account for Research Grants of Athens University (K.L.).

PII: S0015-0282(08)01013-3

doi: 10.1016/j.fertnstert.2008.04.071

Fertility and Sterility
Volume 90, Issue 5 , Pages 2010.e9-2010.e12 , November 2008

Article Tools