Russian Journal of Genetics

, Volume 41, Issue 11, pp 1295–1301 | Cite as

Mutations and Polymorphisms in the Genes for Myocilin and Optineurin as the Risk Factors of Primary Open-Angle Glaucoma

  • V. V. Rakhmanov
  • N. Ya. Nikitina
  • F. M. Zakharova
  • Yu. S. Astakhov
  • M. D. Kvasova
  • V. B. Vasilyev
  • V. I. Golubkov
  • M. Yu. Mandelshtam
Human Genetics


A collection of DNA samples obtained from primary open-angle glaucoma (POAG) patients from St. Petersburg was analyzed for single-strand conformation polymorphism (SSCP) to reveal sequence variants in exon 3 of the myocilin gene (MYOC/TIGR) and in exons 4 and 5 of the optineurin gene (OPTN), where most of the mutations revealed worldwide are located. The Q368X mutation (c. 1102 C → T) in exon 3 of MYOC/TIGR was detected in 1.2% (2/170) of the POAG patients from St. Petersburg, i.e., with the frequency close to that observed in other world populations. Three known polymorphisms in exon 3 of MYOC/TIGR were detected in glaucoma patients, namely Y347Y (c. 1041 T → C) (12.4%), T325T (c. 975 G → A) (0.6%), and K398R (c. 1193 A → G) (0.6%). No statistically significant differences in frequencies of these polymorphisms were revealed between the POAG patient and control groups. The L41L polymorphism (c. 433 G → A) in exon 4 of OPTN was detected in 2.9% of probands and in 1% of controls. The frequency of heterozygotes for the M98K polymorphism (c. 603 T → A) in the OPTN exon 5 was statistically significantly higher (P = 0.036; Fisher's exact test) among the POAG patients (6.5%) than among the controls (1%). In the sample examined the E50K (c. 458G → A) mutation, typical of the patients with pseudonormal intraocular pressure glaucoma (commonly known as low-tension glaucoma, LTG) was not found.


Glaucoma Sequence Variant Intraocular Pressure World Population Glaucoma Patient 
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  1. 1.
    Quigley, H.A., Number of People with Glaucoma Worldwide, Br. J. Ophthalmol., 1996, vol. 80, pp. 389–393.PubMedGoogle Scholar
  2. 2.
    Libman, E.S. and Shakhova, E.V., State and Dynamics of Blindness and Disability Caused by Pathology of the Organ of Vision in Russia, Tezisy dokladov VII s”ezda oftal'mologov Rossii (Proc. VII Meet. of Russian Ophthalmologists), Moscow, 2000, vol. 2, pp. 209–214.Google Scholar
  3. 3.
    Sheffield, V.C., Stone, E.M., Alward, W.L.M., et al., Genetic Linkage of Familial Open Angle Glaucoma to Chromosome 1q21-31, Nat. Genet., 1993, vol. 4, pp. 47–50.CrossRefPubMedGoogle Scholar
  4. 4.
    Nesterov, A.P., Primary Open-Angle Glaucoma: Pathogenesis and Principles of Treatment, Klin. Oftal'mol., 2000, vol. 1, no.1, pp. 4–5.Google Scholar
  5. 5.
    Shields, M.B., Textbook of Glaucoma, Baltimore: Williams & Wilkins, 1987.Google Scholar
  6. 6.
    Wolfs, R.C., Klaver, C.C., Ramrattan, R.S., et al., Genetic Risk of Primary Open-Angle Glaucoma: Population-Based Familial Aggregation Study, Arch. Ophthalmol., 1998, vol. 116, pp. 1640–1645.PubMedGoogle Scholar
  7. 7.
    Stone, E.M., Fingert, J.H., Alward, W.L.M., et al., Identification of a Gene That Causes Primary Open-Angle Glaucoma, Science, 1997, vol. 275, pp. 668–670.PubMedGoogle Scholar
  8. 8.
    Rezaie, T., Child, A., Hitchings, R., et al., Adult-Onset Primary Open-Angle Glaucoma Caused by Mutations in Optineurin, Science, 2002, vol. 295, pp. 1077–1079.CrossRefPubMedGoogle Scholar
  9. 9.
    Faucher, M., Anctil, J.L., Rodrigue, M.A., et al., Founder TIGR/Myocilin Mutations for Glaucoma in the Quebec Population, Hum. Mol. Genet., 2002, vol. 11, pp. 2077–2090.CrossRefPubMedGoogle Scholar
  10. 10.
    Gong, G., Kosoko-Lasaki, O., Haynatzki, G.R., and Wilson, M.R., Genetic Dissection of Myocilin Glaucoma, Hum. Mol. Genet., 2004, vol. 13, pp. 91R–102R.CrossRefGoogle Scholar
  11. 11.
    Alward, W.L., Kwon, Y.H., Kawase, K., et al., Evaluation of Optineurin Sequence Variations in 1048 Patients with Open-Angle Glaucoma, Am. J. Ophthalmol., 2003, vol. 136, pp. 904–910.CrossRefPubMedGoogle Scholar
  12. 12.
    Mandelshtam, M.Yu., Golubkov, V.I., Lamber, E.P., et al., Search for Frequent Mutations in Genes Predisposing to Breast Cancer, Rus. J. Genet., 2001, vol. 37, no.12, pp. 1415–1420.CrossRefGoogle Scholar
  13. 13.
    Sambrook, J., Fritsch, E.F., and Maniatis, T., Molecular Cloning: A Laboratory Manual, Cold Spring Harbor, New York: Cold Spring Harbor Lab., 1989.Google Scholar
  14. 14.
    Fingert, J.H., Heon, E., Liebmann, J.M., et al., Analysis of Myocilin Mutations in 1703 Glaucoma Patients from Five Different Populations, Hum. Mol. Genet., 1999, vol. 8, no.5, pp. 899–905.CrossRefPubMedGoogle Scholar
  15. 15.
    Alward, W.L., Fingert, J.H., Stone, E.M., et al., Clinical Features Associated with Mutations in the Chromosome 1 Open-Angle Glaucoma Gene (GLC1A), New Eng. J. Med., 1998, vol. 338, pp. 1022–1027.PubMedGoogle Scholar
  16. 16.
    Markoff, A., Savov, A., Vladimirov, V., et al., Optimization of Single-Strand Conformational Polymorphism Analysis in the Presence of Polyethylene Glycol, Clin. Chem., 1997, vol. 43, pp. 30–33.PubMedGoogle Scholar
  17. 17.
    Astakhov, Yu.S., Kvasova, M.D., Mandel'shtam, M.Yu., et al., Molecular Genetic Aspects of Primary Open-Angle Glaucoma, Fedorovskie chteniya-2003: Nauchno-prakticheskaya konferentsiya “Sovremennye tekhnologii lecheniya glaukomy” (Moskva, 20–21 iyunya 2003 g.) (Fedorov Course of Lectures-2003: Conf. “Modern Techniques of Treating Glaucoma” (Moscow, June 20–21, 2003), Takhchidi, Kh.P., Ed., Moscow, 2003, pp. 23–25.Google Scholar
  18. 18.
    Jacobson, N., Andrews, M., Shepard, A.R., et al., Non-Secretion of Mutant Proteins of the Glaucoma Gene Myocilin in Cultured Trabecular Meshwork Cells and in Aqueous Humor, Hum. Mol. Genet., 2001, vol. 10, pp. 117–125.CrossRefPubMedGoogle Scholar
  19. 19.
    Liu, Y. and Vollrath, D., Reversal of Mutant Myocilin Non-Secretion and Cell Killing: Implication for Glaucoma, Hum. Mol. Genet., 2004, vol. 13, pp. 1193–1204.CrossRefPubMedGoogle Scholar
  20. 20.
    Jana, N.R., Tanaka, M., Wang, G., and Nukina, N., Polyglutamine Length-Dependent Interaction of Hsp40 and Hsp70 Family Chaperones with Truncated N-Terminal Huntingtin: Their Role in Suppression of Aggregation and Cellular Toxicity, Hum. Mol. Genet., 2000, vol. 9, pp. 2009–2018.CrossRefPubMedGoogle Scholar
  21. 21.
    Vazquez, C.M., Herrero, O.M., Bastus, B.M., et al., Mutations in the Third Exon of the MYOC Gene in Spanish Patients with Primary Open-Angle Glaucoma, Ophthal. Genet., 2000, vol. 21, pp. 109–115.Google Scholar
  22. 22.
    Umeda, T., Matsuo, T., Nagayama, M., et al., Clinical Relevance of Optineurin Sequence Alterations in Japanese Glaucoma Patients, Ophthal. Genet., 2004, vol. 25, no.2, pp. 91–99.Google Scholar
  23. 23.
    Willoughby, C.E., Chan, L.L.Y., Herd, S., et al., Defining the Pathogenicity of Optineurin in Juvenile Open-Angle Glaucoma, Invest. Ophthalmol. Vis. Sci., 2004, vol. 45, pp. 3122–3130.CrossRefPubMedGoogle Scholar
  24. 24.
    Leung, Y.F., Fan, B.J., Lam, D.S.C., et al., Different Optineurin Mutation Pattern in Primary Open-Angle Glaucoma, Invest. Ophthalmol. Vis. Sci, 2003, vol. 44, pp. 3880–3884.PubMedGoogle Scholar
  25. 25.
    Sarfarazi, M. and Rezaie, T., Optineurin in Primary Open-Angle Glaucoma, Ophthalmol. Clin. N. Am., 2003, vol. 16, pp. 529–541.Google Scholar
  26. 26.
    Hattula, K. and Peranen, J., FIP2, a Coiled-Coil Protein, Links Huntingtin to Rab8 and Modulates Cellular Morphogenesis, Curr. Biol., 2000, vol. 10, no.24, pp. 1603–1606.CrossRefPubMedGoogle Scholar

Copyright information

© MAIK "Nauka/Interperiodica" 2005

Authors and Affiliations

  • V. V. Rakhmanov
    • 1
    • 2
  • N. Ya. Nikitina
    • 2
  • F. M. Zakharova
    • 2
  • Yu. S. Astakhov
    • 1
  • M. D. Kvasova
    • 1
  • V. B. Vasilyev
    • 2
  • V. I. Golubkov
    • 2
  • M. Yu. Mandelshtam
    • 2
  1. 1.Department of OphthalmologySt. Petersburg Pavlov State Medical UniversitySt. PetersburgRussia
  2. 2.Institute of Experimental MedicineRussian Academy of Medical SciencesSt. PetersburgRussia

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