Advertisement

European Archives of Oto-Rhino-Laryngology

, Volume 269, Issue 9, pp 2043–2051 | Cite as

No evidence for disturbed COL1A1 and A2 expression in otosclerosis

  • Péter Csomor
  • Balázs Liktor
  • Bálint Liktor
  • István Sziklai
  • Tamás KarosiEmail author
Otology

Abstract

Otosclerosis is a complex bone remodeling disorder of the human otic capsule that might be associated with various mutations of A1 and A2 alleles of type-I collagen. The study herein presented, investigates the possibilty of the genetic involvement of type-I collagen in the pathogenesis of histologically confirmed otosclerosis. A total of 55 ankylotic stapes footplates were analyzed. Cortical bone fragments (n = 30), incus (n = 3) and malleus (n = 2) specimens were employed as negative controls. Specimens were divided into two groups. The first group was processed using conventional H.E. hematoxylin-eosin (H.E.) staining and type-I collagen-specific immunofluorescent assay (IFA), while the second group was examined by COL1A1 and A2-specific RT-PCR. Otosclerotic- (n = 31) and non-otosclerotic stapes footplates (n = 9) as well as cortical bones (n = 20), incus (n = 2) and malleus specimens (n = 1) showed normal and quite similar A1 and A2 allele expression confirmed by IFA. RT-PCR analysis revealed normal and consistent mRNA expression of both alleles in each specimen. Expression levels and patterns of COL1A1/A2 alleles did not show significant correlation with the histological diagnosis of otosclerosis. Type-I collagen is a highly conserved structure protein, which plays a fundamental role in the integritiy of various connective tissues. Mutations of A1 and A2 alleles result in serious systemic disorders of the skeleton, tendons and skin. Since otosclerosis is an organ-specific disease, it is difficult to explain its genetic association with type-I collagen. In conclusion, we found no evidence supporting the putative link of COL1A1 and COL1A2 alleles with otosclerosis.

Keywords

COL1A1 COL1A2 Histology Immunofluorescent assay Otosclerosis RT-PCR 

Notes

Acknowledgments

This work was supported by the Grants of Hungarian Scientific Research Fund (OTKA PD75371, K81480), Mecenatúra Fund of University of Debrecen (DEOEC Mec 17/2008) and Research Fund of European Union (TÁMOP 4.2.1.B).

Conflict of interest

Authors have no conflict of interest.

References

  1. 1.
    Karosi T, Szekanecz Z, Sziklai I (2009) Otosclerosis: an autoimmune disease? Autoimmun Rev 9:95–101PubMedCrossRefGoogle Scholar
  2. 2.
    Chole RA, McKenna M (2001) Pathophysiology of otosclerosis. Otol Neurotol 22:249–257PubMedCrossRefGoogle Scholar
  3. 3.
    Schuknecht HF, Applebaum EL (1969) Surgery for hearing loss. N Engl J Med 280:1154–1160PubMedCrossRefGoogle Scholar
  4. 4.
    Karosi T, Csomor P, Petkó M, Liktor B, Szabó LZ, Pytel J, Jóri J, Sziklai I (2009) Histopathology of nonotosclerotic stapes fixations. Otol Neurotol 30:1058–1066PubMedCrossRefGoogle Scholar
  5. 5.
    Declau F, Van Spaendonck M, Timmermans JP, Michaels L, Liang J, Qiu JP, Van de Heyning P (2001) Prevalence of otosclerosis in an unselected series of temporal bones. Otol Neurotol 22:596–602PubMedCrossRefGoogle Scholar
  6. 6.
    McKenna MJ, Mills BG, Galey FR, Linthicum FH Jr (1986) Filamentous structures morphologically similar to viral nucleocapsids in otosclerotic lesions in two patients. Am J Otol 7:25–28PubMedGoogle Scholar
  7. 7.
    Arnold W, Friedmann I (1988) Otosclerosis—an inflammatory disease of the otic capsule of viral aetiology? J Laryngol Otol 102:865–871PubMedCrossRefGoogle Scholar
  8. 8.
    Ealy M, Smith RJ (2011) Otosclerosis. Adv Otorhinolaryngol 70:122–129PubMedGoogle Scholar
  9. 9.
    Thys M, Van Camp G (2009) Genetics of otosclerosis. Otol Neurotol 30:1021–1032PubMedCrossRefGoogle Scholar
  10. 10.
    Van Den Bogaert K, Govaerts PJ, Schatteman I, Brown MR, Caethoven G, Offeciers FE, Somers T, Declau F, Coucke P, Van de Heyning P, Smith RJ, Van Camp G (2001) A second gene for otosclerosis, OTSC2, maps to chromosome 7q34–36. Am J Hum Genet 68:495–500CrossRefGoogle Scholar
  11. 11.
    Van Den Bogaert K, Govaerts PJ, De Leenheer EM, Schatteman I, Verstreken M, Chen W, Declau F, Cremers CW, Van De Heyning PH, Offeciers FE, Somers T, Smith RJ, Van Camp G (2002) Otosclerosis: a genetically heterogeneous disease involving at least three different genes. Bone 30:624–630CrossRefGoogle Scholar
  12. 12.
    Schrauwen I, Weegerink NJ, Fransen E, Claes C, Pennings RJ, Cremers CW, Huygen PL, Kunst HP, Van Camp G (2011) A new locus for otosclerosis, OTSC10, maps to chromosome 1q41–44. Clin Genet 79:495–497PubMedCrossRefGoogle Scholar
  13. 13.
    McKenna MJ, Kristiansen AG, Bartley ML, Rogus JJ, Haines JL (1998) Association of COL1A1 and otosclerosis: evidence for a shared genetic etiology with mild osteogenesis imperfecta. Am J Otol 19:604–610PubMedGoogle Scholar
  14. 14.
    Lehnerdt G, Unkel C, Metz KA, Jahnke K, Neumann A (2008) Immunohistochemical evidence of BMP-2, -4 and -7 activity in otospongiosis. Acta Otolaryngol 128:13–17PubMedCrossRefGoogle Scholar
  15. 15.
    Thys M, Schrauwen I, Vanderstraeten K, Janssens K, Dieltjens N, Van Den Bogaert K, Fransen E, Chen W, Ealy M, Claustres M, Cremers CR, Dhooge I, Declau F, Claes J, Van de Heyning P, Vincent R, Somers T, Offeciers E, Smith RJ, Van Camp G (2007) The coding polymorphism T263I in TGF-beta1 is associated with otosclerosis in two independent populations. Hum Mol Genet 16:2021–2030PubMedCrossRefGoogle Scholar
  16. 16.
    Karosi T, Szalmás A, Csomor P, Kónya J, Petkó M, Sziklai I (2008) Disease-associated novel CD46 splicing variants and pathologic bone remodeling in otosclerosis. Laryngoscope 118:1669–1676PubMedCrossRefGoogle Scholar
  17. 17.
    Schrauwen I, Ealy M, Huentelman MJ, Thys M, Homer N, Vanderstraeten K, Fransen E, Corneveaux JJ, Craig DW, Claustres M, Cremers CW, Dhooge I, Van de Heyning P, Vincent R, Offeciers E, Smith RJ, Van Camp G (2009) A genome-wide analysis identifies genetic variants in the RELN gene associated with otosclerosis. Am J Hum Genet 84:328–338PubMedCrossRefGoogle Scholar
  18. 18.
    Srivastava TP, Gupta OP (1969) Otosclerosis and osteogenesis and imperfecta. J Laryngol Otol 83:1195–1204PubMedCrossRefGoogle Scholar
  19. 19.
    Chen W, Meyer NC, McKenna MJ, Pfister M, McBride DJ Jr, Fukushima K, Thys M, Camp GV, Smith RJ (2007) Single-nucleotide polymorphisms in the COL1A1 regulatory regions are associated with otosclerosis. Clin Genet 71:406–414PubMedCrossRefGoogle Scholar
  20. 20.
    van Dijk FS, Huizer M, Kariminejad A, Marcelis CL, Plomp AS, Terhal PA, Meijers-Heijboer H, Weiss MM, van Rijn RR, Cobben JM, Pals G (2010) Complete COL1A1 allele deletions in osteogenesis imperfecta. Genet Med 12:736–741PubMedCrossRefGoogle Scholar
  21. 21.
    Bodian DL, Chan TF, Poon A, Schwarze U, Yang K, Byers PH, Kwok PY, Klein TE (2009) Mutation and polymorphism spectrum in osteogenesis imperfecta type II: implications for genotype-phenotype relationships. Hum Mol Genet 18:463–471PubMedCrossRefGoogle Scholar
  22. 22.
    Karsenty G, Park RW (1995) Regulation of type I collagen genes expression. Int Rev Immunol 12:177–185PubMedCrossRefGoogle Scholar
  23. 23.
    Maslen CL, Corson GM, Maddox BK, Glanville RW, Sakai LY (1991) Partial sequence of a candidate gene for the Marfan syndrome. Nature 352:334–337PubMedCrossRefGoogle Scholar
  24. 24.
    Nakanishi G, Shirai M, Kato T, Fujii N, Fujimoto N, Tanaka T, Shirafuji Y, Suzuki N, Otsuka M, Asagoe K, Iwatsuki K, Tanaka R, Fujimoto W, Hanawa F, Shimada S, Nakagawa Y, Tanioka M (2010) Detection of COL1A1-PDGFB fusion transcripts in dermatofibrosarcoma protuberans. Eur J Dermatol 20:528–529PubMedGoogle Scholar
  25. 25.
    McKenna MJ, Kristiansen AG, Tropitzsch AS (2002) Similar COL1A1 expression in fibroblasts from some patients with clinical otosclerosis and those with type I osteogenesis imperfecta. Ann Otol Rhinol Laryngol 111:184–189PubMedGoogle Scholar
  26. 26.
    Clayton AE, Mikulec AA, Mikulec KH, Merchant SN, McKenna MJ (2004) Association between osteoporosis and otosclerosis in women. J Laryngol Otol 118:617–621PubMedCrossRefGoogle Scholar
  27. 27.
    McKenna MJ, Nguyen-Huynh AT, Kristiansen AG (2004) Association of otosclerosis with Sp1 binding site polymorphism in COL1A1 gene: evidence for a shared genetic etiology with osteoporosis. Otol Neurotol 25:447–450PubMedCrossRefGoogle Scholar
  28. 28.
    Rodríguez L, Rodríguez S, Hermida J, Frade C, Sande E, Visedo G, Martín C, Zapata C (2004) Proposed association between the COL1A1 and COL1A2 genes and otosclerosis is not supported by a case-control study in Spain. Am J Med Genet A 128:19–22CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Péter Csomor
    • 1
  • Balázs Liktor
    • 2
  • Bálint Liktor
    • 2
  • István Sziklai
    • 1
  • Tamás Karosi
    • 1
    Email author
  1. 1.Department of Otolaryngology and Head and Neck Surgery, Medical and Health Science CenterUniversity of DebrecenDebrecenHungary
  2. 2.Department of OtolaryngologyBajcsy-Zsilinszky HospitalBudapestHungary

Personalised recommendations