Human Genetics

, Volume 110, Issue 1, pp 52–56

A major marker for normal tension glaucoma: association with polymorphisms in the OPA1 gene

  • Tin Aung
  • Louise Ocaka
  • Neil D. Ebenezer
  • Alex G. Morris
  • Michael Krawczak
  • Dawn L. Thiselton
  • Christiane Alexander
  • Marcela Votruba
  • Glen Brice
  • Anne H. Child
  • Peter J. Francis
  • Roger A. Hitchings
  • Ordan J. Lehmann
  • Shomi S. Bhattacharya
Original Investigation

DOI: 10.1007/s00439-001-0645-7

Cite this article as:
Aung, T., Ocaka, L., Ebenezer, N.D. et al. Hum Genet (2002) 110: 52. doi:10.1007/s00439-001-0645-7

Abstract.

Normal tension glaucoma (NTG) is a major form of glaucoma, associated with intraocular pressures that are within the statistically normal range of the population. OPA1, the gene responsible for autosomal dominant optic atrophy represents an excellent candidate gene for NTG, as the clinical phenotypes are similar and OPA1 is expressed in the retina and optic nerve. Eighty-three well-characterized NTG patients were screened for mutations in OPA1 by heteroduplex analysis and bi-directional sequencing. Sequences found to be altered in NTG subjects were examined for variations in 100 population controls. A second cohort of 80 NTG patients and 86 population controls was subsequently screened to determine whether the initial findings could be replicated. A single nucleotide polymorphism (SNP) on intervening sequence (IVS) 8 (IVS8 + 4 C/T) was found to be strongly associated with the occurrence of NTG in both cohorts (χ2=7.97, P=0.005 in the first cohort, χ2=9.93, P=0.002 in the second cohort; odds ratio 3.1 (95% CI: 1.8–5.6). A second SNP (IVS8 + 32 T/C) appeared to be associated with disease in the first cohort (χ2=4.71, P=0.030), but this finding could not be replicated in the second cohort. In the combined cohort, the compound at-risk genotype IVS8 + 4 C/T, + 32 T/C was strongly associated with the occurrence of NTG (χ2=22.04, P=0.00001 after correcting for testing four genotypes). These results indicate that polymorphisms in the OPA1 gene are associated with NTG and may be a marker for the disease.

Copyright information

© Springer-Verlag 2001

Authors and Affiliations

  • Tin Aung
    • 1
  • Louise Ocaka
    • 1
  • Neil D. Ebenezer
    • 1
  • Alex G. Morris
    • 1
  • Michael Krawczak
    • 4
  • Dawn L. Thiselton
    • 1
  • Christiane Alexander
    • 1
  • Marcela Votruba
    • 1
  • Glen Brice
    • 2
  • Anne H. Child
    • 2
  • Peter J. Francis
    • 1
  • Roger A. Hitchings
    • 2
  • Ordan J. Lehmann
    • 1
  • Shomi S. Bhattacharya
    • 1
  1. 1.Department of Molecular Genetics, Institute of Ophthalmology, University College London, Bath Street, London EC1V 9EL, UKUK
  2. 2.Moorfields Eye Hospital, London, UKUK
  3. 3.Singapore National Eye Centre, SingaporeSingapore
  4. 4.Institute of Medical Genetics, University of Wales College of Medicine, Cardiff, UKUK
  5. 5.St George's Hospital Med School, London, UKUK