A major marker for normal tension glaucoma: association with polymorphisms in the OPA1 gene
| Autor: | Anne H. Child, Christiane Alexander, Shomi S. Bhattacharya, Alex G. Morris, Louise Ocaka, G Brice, Ordan J. Lehmann, Marcela Votruba, Tin Aung, Roger A. Hitchings, Peter J. Francis, Neil D. Ebenezer, Michael Krawczak, Dawn L. Thiselton |
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| Rok vydání: | 2002 |
| Předmět: |
Genetic Markers
medicine.medical_specialty Candidate gene Genotype genetic structures Population Single-nucleotide polymorphism Biology Polymorphism Single Nucleotide Retina White People Cohort Studies Reference Values Internal medicine Normal tension glaucoma London Genetics medicine Humans education Genetics (clinical) education.field_of_study Polymorphism Genetic Base Sequence Glaucoma Optic Nerve Odds ratio Phosphoproteins eye diseases Endocrinology Genetic marker Cohort Microtubule Proteins Stathmin sense organs |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| Popis: | 5 páginas, 2 figuras, 2 tablas.-- et al. 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 (L2=7.97, P=0.005 in the first cohort, L2=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 (L2=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 (L2=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. The work was supported in part by the International Glaucoma Association and Moorfields Special Trustees, and an equipment grant from the Glaucoma Research Foundation. Dr Aung is supported by the National Medical Research Council of Singapore and the Singapore National Eye Centre, Mr Brice by the Royal National Institute for the Blind and Dr Child by the Bluff-Field Charitable Trust and the IGA. |
| Databáze: | OpenAIRE |
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