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The plasminogen activator inhibitor-1 (PAI-1) gene −844 A/G and −675 4G/5G promoter polymorphism significantly influences plasma PAI-1 levels in women with polycystic ovary syndrome

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Abstract

Mutations in the plasminogen activator inhibitor-1 (PAI-1) gene, along with increased PAI-1 levels, have been implicated in the pathogenesis of polycystic ovarian syndrome (PCOS). We investigated a possible influence of the promoter polymorphism (−844 A/G and −675 4G/5G) in the PAI-1 gene on plasma PAI-1 levels in 126 PCOS patients and 97 healthy controls. Levels of total testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH), fasting plasma glucose (FPG), fasting insulin, and PAI-1 were measured, and body mass index (BMI), waist-to-hip ratio (WHR), LH/FSH ratio, and homeostasis model assessment for insulin resistance (HOMA-IR) were calculated. PAI-1 −675 4G/5G and −844 A/G gene polymorphisms were also performed. Total testosterone, fasting insulin, and PAI-1 levels; BMI, LH/FSH, and HOMA-IR were significantly higher in PCOS patients than controls (P < 0.05). The odds ratio of 4G/4G genotype, 4G allele, and the combination genotype of 4G/4G and −844 A/A were 2.49 (95% confidence interval (CI), 1.4–4.44), 2.1 (95% CI, 1.43–3.08), and 2.9 (95% CI, 1.41–5.98), respectively, (P < 0.001). In the PCOS group, the PAI-1 level of the A/A was significantly higher than that of the A/G or G/G genotype, similarly was 4G/4G genotype compared with 4G/5G or 5G/5G genotype. The plasma PAI-1 levels of the combination of the PAI-1 −844 A/A and −675 4G/4G or 4G/5G genotypes, or the coadunation of 4G/4G and −844 non-G/G (A/A + A/G) genotypes were significantly high in PCOS women compared with controls. A trend to a positive interaction between PAI-1 −675 4G/5G and −844 A/G gene polymorphism may elevate plasma PAI-1 levels and hypofibrinolysis, which is probably an important hereditary risk factor in PCOS.

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References

  1. D.A. Ehrmann, D.R. Liljenquist, K. Kasza, R. Azziz, R.S. Legro, M.N. Ghazzi, J. Clin. Endocrinol. Metab. 91(1), 48–53 (2006)

    Article  CAS  PubMed  Google Scholar 

  2. S.I. McFarlane, M. Banerji, J.R. Sowers, J. Clin. Endocrinol. Metab. 86(2), 713–718 (2001)

    Article  CAS  PubMed  Google Scholar 

  3. E. Diamanti-Kandarakis, H. Kandarakis, R.S. Legro, Endocrine 30(1), 19–26 (2006)

    Article  CAS  PubMed  Google Scholar 

  4. S. Franks, N. Gharani, D. Waterworth et al., Hum. Reprod. 12(12), 2641–2648 (1997)

    Article  CAS  PubMed  Google Scholar 

  5. P. Eriksson, B. Kallin, F.M. van’t Hooft, P. Båvenholm, A. Hamsten, Proc. Natl Acad. Sci. USA 92(6), 1851–1855 (1995)

    Article  CAS  PubMed  Google Scholar 

  6. M. Sampson, C. Kong, A. Patel, R. Unwin, H.S. Jacobs, Clin. Endocrinol. (Oxf) 45(5), 623–629 (1996)

    Article  CAS  Google Scholar 

  7. E. Diamanti-Kandarakis, G. Palioniko, K. Alexandraki, A. Bergiele, T. Koutsouba, M. Bartzis, Eur. J. Endocrinol. 150(6), 793–798 (2004)

    Article  CAS  PubMed  Google Scholar 

  8. I. Tarkun, Z. Cantürk, B.C. Arslan, E. Türemen, P. Tarkun, Endocr. J. 51(5), 467–472 (2004)

    Article  CAS  PubMed  Google Scholar 

  9. W.U. Atiomo, S.A. Bates, J.E. Condon, S. Shaw, J.H. West, A.G. Prentice, Fertil. Steril. 69(2), 236–241 (1998)

    Article  CAS  PubMed  Google Scholar 

  10. S. Kathiresan, S.B. Gabriel, Q. Yang et al., Circulation 112(12), 1728–1735 (2005)

    Article  CAS  PubMed  Google Scholar 

  11. M. Verschuur, A. Jellema, E.M. Bladbjerg et al., Atherosclerosis 181(2), 275–284 (2005)

    Article  CAS  PubMed  Google Scholar 

  12. S. Saidi, L.B. Slamia, T. Mahjoub, S.B. Ammou, W.Y. Almawi, J. Stroke Cerebrovasc. Dis. 16(4), 153–159 (2007)

    Article  PubMed  Google Scholar 

  13. N. Grubic, M. Stegnar, P. Peternel, A. Kaider, B.R. Binder, Thromb. Res. 84(6), 431–443 (1996)

    Article  CAS  PubMed  Google Scholar 

  14. Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group, Fertil. Steril. 81(1), 19–25 (2004)

    Article  Google Scholar 

  15. C.M. DeUgarte, A.A. Bartolucci, R. Azziz, Fertil. Steril. 83(5), 1454–1460 (2005)

    Article  CAS  PubMed  Google Scholar 

  16. N.M. Torres-Carrillo, N. Torres-Carrillo, M.V.-D. Mercado et al., Rheumatol. Int. 28(4), 355–360 (2008)

    Article  CAS  PubMed  Google Scholar 

  17. C.J. Glueck, P. Wang, R.N. Fontaine, L. Sieve-Smith, T. Tracy, S.K. Moore, Metabolism 48(12), 1589–1595 (1999)

    Article  CAS  PubMed  Google Scholar 

  18. C.J. Glueck, H. Phillips, D. Cameron et al., Metabolism 49(7), 845–852 (2000)

    Article  CAS  PubMed  Google Scholar 

  19. W.U. Atiomo, R. Fox, J.E. Condon et al., Clin. Endocrinol. (Oxf) 52(4), 487–492 (2000)

    Article  CAS  Google Scholar 

  20. L. Fu, H. Jin, K. Song, C. Zhang, J. Shen, Y. Huang, Chin. Med. J. (Engl.) 114(3), 266–269 (2001)

    CAS  Google Scholar 

  21. A. Haselbauer, W. Haberbosch, H. Tillmanns, A. Gardemann, Thromb. Haemost. 88(4), 697–698 (2002)

    PubMed  Google Scholar 

  22. B. Smolarz, J. Blasiak, A. Kulig et al., J. Exp. Clin. Cancer Res. 20(2), 247–252 (2001)

    CAS  PubMed  Google Scholar 

  23. P.E. Morange, M. Henry, D. Tregouët et al., Arterioscler. Thromb. Vasc. Biol. 20(5), 1387–1391 (2000)

    CAS  PubMed  Google Scholar 

  24. D. Fabbro, A.V. D’Elia, R. Spizzo et al., Gynecol. Obstet. Invest. 56(1), 17–22 (2003)

    Article  CAS  PubMed  Google Scholar 

  25. S. Dawson, A. Henney, Atherosclerosis 95(2–3), 105–117 (1992)

    Article  CAS  PubMed  Google Scholar 

  26. L. Tiret, P. Amouyel, R. Rakotovao, F. Cambien, P. Ducimetière, Am. J. Hum. Genet. 48(5), 926–934 (1991)

    CAS  PubMed  Google Scholar 

  27. S.J. Dawson, B. Wiman, A. Hamsten, F. Green, S. Humphries, A.M. Henney, J. Biol. Chem. 268(15), 10739–10745 (1993)

    CAS  PubMed  Google Scholar 

  28. M. Henry, D.A. Tregouët, M.C. Alessi et al., Arterioscler. Thromb. Vasc. Biol. 18(1), 84–91 (1998)

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This research was funded in part by the National Natural Science Foundation of China (No. 30240037) and Post-graduate New Ideas Foundation of Harbin Medical University (N0.200601176). We are very grateful to our patients for their participation in this study.

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Authors and Affiliations

  1. Department of Reproductive Endocrinology, The First Affiliated Hospital of Harbin Medical University, No. 23 YouZheng Street, Harbin, 150001, Heilongjiang, China

    Sun Lin, Zhang Huiya, Liu Bo, Wei Wei & Guan Yongmei

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  1. Sun Lin
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  2. Zhang Huiya
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  3. Liu Bo
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  4. Wei Wei
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  5. Guan Yongmei
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Correspondence to Guan Yongmei.

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Lin, S., Huiya, Z., Bo, L. et al. The plasminogen activator inhibitor-1 (PAI-1) gene −844 A/G and −675 4G/5G promoter polymorphism significantly influences plasma PAI-1 levels in women with polycystic ovary syndrome. Endocr 36, 503–509 (2009). https://doi.org/10.1007/s12020-009-9255-2

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  • DOI: https://doi.org/10.1007/s12020-009-9255-2

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