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Androgen receptor (CAG)n polymorphism and androgen levels in women with systemic lupus erythematosus and healthy controls

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Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disorder that affects mainly females. Therefore, interrelations between the reproductive and immune system have been assumed. Considering the complex influence of hormones and receptors, we aimed to investigate the influence of androgens and androgen receptor (AR) polymorphism in women with SLE. One hundred and sixteen patients and 44 healthy women were investigated. Testosterone, sex hormone-binding globulin (SHBG), dehydroepiandrosterone-sulphate (DHEAS) concentrations and AR (CAG)n polymorphism were determined. SLE patients had significantly lower levels of total and free testosterone and DHEAS in comparison with the controls. No differences in the CAG repeat length between the groups were established. Women with two alleles carrying more than 22 CAG repeats had significantly higher levels of SHBG (101.51 ± 61.81 vs. 69.22 ± 45.93 nmol/l, p = 0.015) and DHEAS (3.11 ± 2.65 vs. 2.11 ± 3.06 μmol/l, p = 0.007) and a tendency to higher testosterone concentrations (2.35 ± 2.10 vs. 1.71 ± 1.70 nmol/l, p = 0.056) in comparison with other women. The CAG repeat length in the relatively longer (CAG)n allele was inversely related to the Systemic Lupus International Collaborating Clinics/ACR index (r = −0.258, p = 0.009). In conclusion, the androgen receptor (CAG)n polymorphism is not related to the development of SLE, but it could modulate the severity of the lupus chronic damages as well as the androgen levels in women.

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References

  1. Cervera R, Espinosa G, D’Cruz D (2009) Systemic lupus erythematosus: pathogenesis, clinical manifestations and diagnosis. In: Bijlsma JW (ed) EULAR compendium on rheumatic diseases. BMJ Publishing Group and European League Against Rheumatism, London, pp 257–268

    Google Scholar 

  2. Cutolo M, Sulli A, Capellino S et al (2004) Sex hormones influence on the immune system: basic and clinical aspects of autoimmunity. Lupus 13:635–638

    Article  PubMed  CAS  Google Scholar 

  3. Kanda N, Tsuchida T, Tamaki K (1997) Testosterone suppresses anti-DNA antibody production in peripheral blood mononuclear cells from patients with systemic lupus erythematosus. Arthritis Rheum 40:1703–1711

    Article  PubMed  CAS  Google Scholar 

  4. Walker SE, Besch-Williford CL, Keisler DH (1994) Accelerated deaths from systemic lupus erythematosus in NZB × NZW F1 mice treated with the testosterone-blocking drug flutamide. J Lab Clin Med 124:401–407

    PubMed  CAS  Google Scholar 

  5. Palazzolo I, Gliozzi A, Rusmini P et al (2008) The role of the polyglutamine tract in androgen receptor. J Steroid Biochem Mol Biol 108:245–253

    Article  PubMed  CAS  Google Scholar 

  6. Simanainen U, Brogley M, Gao YR et al (2011) Length of the human androgen receptor glutamine tract determines androgen sensitivity in vivo. Mol Cell Endocrinol 342:81–86

    Article  PubMed  CAS  Google Scholar 

  7. La Spada AP, Wilson EM, Lubahn DB, Harding AE, Fischbeck KH (1991) Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy. Nature 352:77–79

    Article  PubMed  Google Scholar 

  8. Hochberg MC (1997) Updating the American College of Rheumatology revised criteria for classification of systemic lupus erythematosus. Arthritis Rheum 40:1725

    Article  PubMed  CAS  Google Scholar 

  9. Stoll T, Seifert B, Isenberg DA (1996) SLICC/ACR damage index is valid, and renal and pulmonary organ scores are predictors of severe outcome in patients with systemic lupus erythematosus. Br J Rheumatol 35:248–254

    Article  PubMed  CAS  Google Scholar 

  10. Gladman D, Ginzler E, Goldsmith C et al (1996) The development and initial validation of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index for systemic lupus erythematosus. Arthritis Rheum 39:363–369

    Article  PubMed  CAS  Google Scholar 

  11. Bombardier C, Gladman DD, Urowitz MB, Caron D, Chang CH (1992) Derivation of the SLEDAI. A disease activity index for lupus patients, The committee on Prognosis Studies in SLE. Arthritis Rheum 35:630–640

    Article  PubMed  CAS  Google Scholar 

  12. Vermeulen A, Verdonck L, Kaufman JM (1999) A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab 84:3666–3672

    Article  PubMed  CAS  Google Scholar 

  13. Lyon MF (1988) The William Allan memorial award address: X-chromosome inactivation and the location and expression of X-linked genes. Am J Hum Genet 42:8–16

    PubMed  CAS  Google Scholar 

  14. Hickey T, Chandy A, Norman RJ (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

    Article  PubMed  CAS  Google Scholar 

  15. Westberg L, Baghaei F, Rosmond R et al (2001) Polymorphisms of the androgen receptor gene and the estrogen receptor beta gene are associated with androgen levels in women. J Clin Endocrinol Metab 86:2562–2568

    Article  PubMed  CAS  Google Scholar 

  16. Fehér KG, Bencze G, Ujfalussy J, Fehér T (1987) Serum steroid hormone levels in systemic lupus erythematosus (SLE). Acta Med Hung 44:321–327

    PubMed  Google Scholar 

  17. Lahita RG, Bradlow HL, Ginzler E, Pang S, New M (1987) Low plasma androgens in women with systemic lupus erythematosus. Arthritis Rheum 30:241–248

    Article  PubMed  CAS  Google Scholar 

  18. Folomeev M, Dougados M, Beaune J et al (1992) Plasma sex hormones and aromatase activity in tissues of patients with systemic lupus erythematosus. Lupus 1:191–195

    Article  PubMed  CAS  Google Scholar 

  19. Navarro MA, Vidaller A, Ortolá JB, Bonnin MR, Pac MV, Moga I (1992) Salivary testosterone levels in women with systemic lupus erythematosus. Arthritis Rheum 35:557–559

    Article  PubMed  CAS  Google Scholar 

  20. Muñoz JA, Gil A, López-Dupla JM, Vázquez JJ, González-Gancedo P (1994) Sex hormones in chronic systemic lupus erythematosus. Correlation with clinical and biological parameters. Ann Med Interne (Paris) 145:459–463

    Google Scholar 

  21. Speroff L, Fritz M (2005) Hormone biosynthesis, metabolism and mechanism of action. In: Fritz M, Speroff L (eds) Clinical gynecologic endocrinology and infertility. Lippincot Williams & Willkins, Philadelphia, pp 25–96

    Google Scholar 

  22. Rizzo L, Dobrovsky V, Danilowicz K et al (2007) Low-dose glucocorticoids in hyperandrogenism. Medicina (B Aires) 67:247–252

    CAS  Google Scholar 

  23. Huhtaniemi IT, Pye SR, Limer KL et al European Male Ageing Study Group (2009) Increased estrogen rather than decreased androgen action is associated with longer androgen receptor CAG repeats. J Clin Endocrinol Metab 94:277–284

    Google Scholar 

  24. Jääskeläinen J, Korhonen S, Kuulasmaa T et al (2008) Androgen receptor gene CAG repeat length in women with metabolic syndrome. Gynecol Endocrinol 24:411–416

    Article  PubMed  Google Scholar 

  25. Brum IS, Spritzer PM, Paris F, Maturana MA, Audran F, Sultan C (2005) Association between androgen receptor gene CAG repeat polymorphism and plasma testosterone levels in postmenopausal women. J Soc Gynecol Investig 12:135–141

    Article  PubMed  CAS  Google Scholar 

  26. Kim JJ, Choung SH, Choi YM, Yoon SH, Kim SH, Moon SY (2008) Androgen receptor gene CAG repeat polymorphism in women with polycystic ovary syndrome. Fertil Steril 90:2318–2323

    Article  PubMed  CAS  Google Scholar 

  27. Van Nieuwerburgh F, Stoop D, Cabri P, Dhont M, Deforce D, De Sutter P (2008) Shorter CAG repeats in the androgen receptor gene may enhance hyperandrogenicity in polycystic ovary syndrome. Gynecol Endocrinol 24:669–673

    Article  PubMed  Google Scholar 

  28. Nenonen H, Björk C, Skjaerpe PA, Giwercman A, Rylander L, Svartberg J, Giwercman YL (2010) CAG repeat number is not inversely associated with androgen receptor activity in vitro. Mol Hum Reprod 16:153–157

    Article  PubMed  CAS  Google Scholar 

  29. Davis-Dao C, Koh CJ, Hardy BE, Chang A et al (2012) Shorter androgen receptor CAG repeat lengths associated with cryptorchidism risk among Hispanic white boys. J Clin Endocrinol Metab 97:E393–E399

    Article  PubMed  CAS  Google Scholar 

  30. Tanriverdi F, Silveira LF, MacColl GS, Bouloux PM (2003) The hypothalamic–pituitary–gonadal axis: immune function and autoimmunity. J Endocrinol 176:293–304

    Article  PubMed  CAS  Google Scholar 

  31. Rahman F, Christian HC (2007) Non-classical actions of testosterone: an update. Trends Endocrinol Metab 18:371–378

    Article  PubMed  CAS  Google Scholar 

  32. Tessnow AH, Olsen NJ, Kovacs WJ (2011) Expression of humoral autoimmunity is related to androgen receptor CAG repeat length in men with systemic lupus erythematosus. J Clin Immunol 31:567–573

    Article  PubMed  CAS  Google Scholar 

  33. Deng Y, Grossman JM, Fu Q et al (2011) Association of androgen receptor gene polymorphism with damage in systemic lupus erythematosus. In: ACR/ARHP annual scientific meeting 11 (abstract 640)

  34. Saltiki K, Cimponeriu A, Garofalaki M et al (2011) Severity of coronary artery disease in postmenopausal women: association with the androgen receptor gene (CAG)n repeat polymorphism. Menopause 18:1225–1231

    Article  PubMed  Google Scholar 

  35. Zitzmann M, Brune M, Kornmann B et al (2001) The CAG repeat polymorphism in the AR gene affects high density lipoprotein cholesterol and arterial vasoreactivity. J Clin Endocrinol Metab 86:4867–4873

    Article  PubMed  CAS  Google Scholar 

  36. Pausova Z, Abrahamowicz M, Mahboubi A et al (2010) Functional variation in the androgen-receptor gene is associated with visceral adiposity and blood pressure in male adolescents. Hypertension 55:706–714

    Article  PubMed  CAS  Google Scholar 

  37. Kuliczkowski W, Filus A, Kuliczkowska-Plaksej J et al (2010) Androgen receptor polymorphism and platelet reactivity in healthy men. Thromb Res 126:65–67

    Article  Google Scholar 

Download references

Acknowledgments

This study was financially supported by MU, Sofia (Grant 26/2010), by the Bulgarian society for osteoporosis and osteoarthritis and by the EU Program “Development of human resources—Science and business,” № BG051PO001-3.3-05/0001. The authors declare that there is no conflict of interests.

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Authors and Affiliations

  1. Clinical Center of Endocrinology and Gerontology, USBALE, Medical University, Faculty of Medicine, Sofia, 2, Zdrave Str., Sofia, 1431, Bulgaria

    Ralitsa Robeva, Georgi Kirilov, Analia Tomova & Philip Kumanov

  2. Clinic of Rheumatology, Medical University, Faculty of Medicine, Sofia, 13, Urvich Str., Sofia, 1612, Bulgaria

    Dobromir Tanev, Rasho Rashkov & Zlatimir Kolarov

  3. National Genetic Laboratory, USHATOG “Maichin dom”, Medical University, Faculty of Medicine, Sofia, 2, Zdrave Str., Sofia, 1431, Bulgaria

    Silvia Andonova & Alexey Savov

  4. Section of Medical Informatics and Biostatistics, Department of Social Medicine and Health Management, Medical University, Sofia, 8, Bjalo more Str., Sofia, 1527, Bulgaria

    Milena Stoycheva

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  1. Ralitsa Robeva
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  2. Dobromir Tanev
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  3. Silvia Andonova
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Correspondence to Ralitsa Robeva or Zlatimir Kolarov.

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Robeva, R., Tanev, D., Andonova, S. et al. Androgen receptor (CAG)n polymorphism and androgen levels in women with systemic lupus erythematosus and healthy controls. Rheumatol Int 33, 2031–2038 (2013). https://doi.org/10.1007/s00296-013-2687-2

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  • DOI: https://doi.org/10.1007/s00296-013-2687-2

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