Ceren HANGÜL
(Akdeniz Üniversite, Biyoloji ve Genetik Tıp Bölümü, Antalya, Türkiye)
Selen BOZKURT
(Akdeniz Üniversite, Biyoistatistik Bölümü, Antalya, Türkiye)
Uğur BİLGE
(Akdeniz Üniversite, Biyoistatistik Bölümü, Antalya, Türkiye)
Sebahat ÖZDEM
(Akdeniz Üniversite, Biyokimya Bölümü, Antalya, Türkiye)
Hasan Ali ALTUNBAŞ
(Akdeniz Üniversite, Tıp Fakültesi, Endokrinoloji Bölümü, Antalya, Türkiye)
Hilmi UYSAL
(Akdeniz Üniversite, Tıp Fakültesi, Nöroloji Bölümü, Antalya, Türkiye)
Ayşe Filiz KOÇ
(Çukurova Üniversitesi, Tıp Fakültesi, Nöroloji Anabilim Dalı, Adana, Türkiye)
Sibel BERKER KARAÜZÜM
(Akdeniz Üniversite, Tıp Fakültesi, Biyoloji ve Genetik Tıp Bölümü, Antalya, Türkiye)
Yıl: 2020Cilt: 37Sayı: 4ISSN: 1300-1817 / 2636-865XSayfa Aralığı: 190 - 196İngilizce

18 0
The Ratios of Estradiol and Progesterone to Testosterone Influence the Severity of Facioscapulohumeral Muscular Dystrophy
Background: Facioscapulohumeral muscular dystrophy (FSHD) occurs as a consequence of genetic deletion of D4Z4 repeats on chromosome 4q35. Onset of FSHD is earlier in males, suggesting that testosterone may trigger the disease. In accordance, the rapid progression of disease in women after menopause suggests a protective role for estrogen and progesterone. No studies have examined levels of all these hormones in relation with the severity of FSHD. Aims: To evaluate the possible correlation between the severity of FSHD with sex hormones, age, and genetic deletion on chromosome 4q35. Subjects and Methods: D4Z4 repeat units were investigated in 33 patients (19 males/14 females) with FSHD. In the blood samples, luteinizing hormone, follicle-stimulating hormone, free estriol, estradiol, free testosterone and total testosterone, progesterone, 17-OH progesterone, prolactin, albumin, and fibrinogen were measured. The severity of FSHD was identified using a Clinical Severity Score (CSS) scaling system. Spearman’s correlation and regression analyses were performed as statistical analyses. Results: Age (P = 0.001, r = 0.541) and total testosterone (P = 0.045, r = 0.351) were positively correlated, and the progesterone/total testosterone (P = 0.025, r = −0.390) and estradiol/total testosterone ratios (P = 0.025, r = −0.389) were negatively correlated with the severity of FSHD. Conclusions: Our results indicate that age, total testosterone, ratios of estradiol and progesterone to total testosterone, but not deletion on chromosome 4q35, have a significant relation with the severity of FSHD. Given that both estrogen and testosterone treatment are considered in therapy, our results suggest that estrogen and progesterone but not testosterone are likely to be more effective on the severity of FSHD.
DergiDiğerErişime Açık
  • 1. Statland J, Tawil R. Facioscapulohumeral muscular dystrophy. Neurol Clin 2014;32:721-8, ix.
  • 2. Hewitt JE, Lyle R, Clark LN, Valleley EM, Wright TJ, Wijmenga C, et al. Analysis of the tandem repeat locus D4Z4 associated with facioscapulohumeral muscular dystrophy. Hum Mol Genet 1994;3:1287-95.
  • 3. de Greef JC, Lemmers RJ, van Engelen BG, Sacconi S, Venance SL, Frants RR, et al. Common epigenetic changes of D4Z4 in contraction-dependent and contraction-independent FSHD. Hum Mutat 2009;30:1449-59.
  • 4. Yamanaka G, Goto K, Ishihara T, Oya Y, Miyajima T, Hoshika A, et al. FSHD-like patients without 4q35 deletion. J Neurol Sci 2004;219:89-93.
  • 5. Hamanaka K, Sikrova D, Mitsuhashi S, Masuda H, Sekiguchi Y, Sugiyama A, et al. Homozygous nonsense variant in LRIF1 associated with facioscapulohumeral muscular dystrophy. Neurology. 2020;94:e2441-7.
  • 6. Pandya S, King WM, Tawil R. Facioscapulohumeral dystrophy. Phys Ther 2008;88:105-13.
  • 7. Fitzsimons RB. Retinal vascular disease and the pathogenesis of facioscapulohumeral muscular dystrophy. A signalling message from Wnt? Neuromuscul Disord 2011;21:263-71.
  • 8. Zatz M, Marie SK, Cerqueira A, Vainzof M, Pavanello RC, Passos-Bueno MR. The facioscapulohumeral muscular dystrophy (FSHD1) gene affects males more severely and more frequently than females. Am J Med Genet 1998;77:155-61.
  • 9. Tonini MM, Passos-Bueno MR, Cerqueira A, Matioli SR, Pavanello R, Zatz M. Asymptomatic carriers and gender differences in facioscapulohumeral muscular dystrophy (FSHD). Neuromuscul Disord 2004;14:33-8.
  • 10. Puma A, Garibaldi M, Teveroni E, Deidda G, Moretti FS. Estrogens as a Potential Disease Modifier in FSHD: A Retrospective Clinical Study; 2017.
  • 11. Mul K, Horlings CG, Voermans NC, Schreuder TH, van Engelen BG. Lifetime endogenous estrogen exposure and disease severity in female patients with facioscapulohumeral muscular dystrophy. Neuromuscul Disord 2018;28:508-11.
  • 12. Teveroni E, Pellegrino M, Sacconi S, Calandra P, Cascino I, Farioli-Vecchioli S, et al. Estrogens enhance myoblast differentiation in facioscapulohumeral muscular dystrophy by antagonizing DUX4 activity. J Clin Invest 2017;127:1531-45.
  • 13. Banerji CR, Panamarova M, Pruller J, Figeac N, Hebaishi H, Fidanis E, et al. Dynamic transcriptomic analysis reveals suppression of PGC1 alpha/ERR alpha drives perturbed myogenesis in facioscapulohumeral muscular dystrophy. Human Molecular Genetics 2019;28:1244-59.
  • 14. Ricci E, Galluzzi G, Deidda G, Cacurri S, Colantoni L, Merico B, et al. Progress in the molecular diagnosis of facioscapulohumeral muscular dystrophy and correlation between the number of KpnI repeats at the 4q35 locus and clinical phenotype. Ann Neurol 1999;45:751-7.
  • 15. van Overveld PG, Enthoven L, Ricci E, Rossi M, Felicetti L, Jeanpierre M, et al. Variable hypomethylation of D4Z4 in facioscapulohumeral muscular dystrophy. Ann Neurol 2005;58:569-76.
  • 16. Tawil R, Forrester J, Griggs RC, Mendell J, Kissel J, McDermott M, et al. Evidence for anticipation and association of deletion size with severity in facioscapulohumeral muscular dystrophy. The FSH-DY Group. Ann Neurol 1996;39:744-8.
  • 17. Statland JM, Donlin-Smith CM, Tapscott SJ, Lemmers RJ, van der Maarel SM, Tawil R. Milder phenotype in facioscapulohumeral dystrophy with 7-10 residual D4Z4 repeats. Neurology 2015;85:2147-50.
  • 18. Klinge L, Eagle M, Haggerty ID, Roberts CE, Straub V, Bushby KM. Severe phenotype in infantile facioscapulohumeral muscular dystrophy. Neuromuscul Disord 2006;16:553-8.
  • 19. Butz M, Koch MC, Müller-Felber W, Lemmers RJ, van der Maarel SM, Schreiber H. Facioscapulohumeral muscular dystrophy. Phenotype-genotype correlation in patients with borderline D4Z4 repeat numbers. J Neurol 2003;250:932-7.
  • 20. van Overveld PG, Lemmers RJ, Sandkuijl LA, Enthoven L, Winokur ST, Bakels F, et al. Hypomethylation of D4Z4 in 4q-linked and non-4q-linked facioscapulohumeral muscular dystrophy. Nat Genet 2003;35:315-7.
  • 21. Salsi V, Magdinier F, Tupler R. Does DNA methylation matter in FSHD? Genes (Basel) 2020;11:258.
  • 22. Mul K, van den Boogaard ML, van der Maarel SM, van Engelen BG. Integrating clinical and genetic observations in facioscapulohumeral muscular dystrophy. Curr Opin Neurol 2016;29:606-13.
  • 23. Young JM, Whiddon JL, Yao Z, Kasinathan B, Snider L, Geng LN, et al. DUX4 binding to retroelements creates promoters that are active in FSHD muscle and testis. PLoS Genet 2013;9:e1003947.
  • 24. Heatwole CR. Study of Testosterone and rHGH in FSHD: A Proofof-Concept Study. 2017-2021. Available from: http://grantome.com/ grant/NIH/R01-NS095813-01A1. [Last accessed on 2020 Jan 24].
  • 25. Sacconi S, Salviati L, Desnuelle C. Facioscapulohumeral muscular dystrophy. Biochim Biophys Acta 2015;1852:607-14.
  • 26. Jiroutek MR, Chen MH, Johnston CC, Longcope C. Changes in reproductive hormones and sex hormone-binding globulin in a group of postmenopausal women measured over 10 years. Menopause 1998;5:90-4.

TÜBİTAK ULAKBİM Ulusal Akademik Ağ ve Bilgi Merkezi Cahit Arf Bilgi Merkezi © 2019 Tüm Hakları Saklıdır.