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Abstract #18548 Published in IGR 3-3
Association of a single nucleotide polymorphism in the TIGR/Myocilin gene promoter with the severity of primary open-angle glaucoma
Colomb E; Nguyen TD; Bechetoille A; Dascotte JC; Valtot F; Brezin AP; Berkani M; Copin B; Gomez L; Polansky JRClinical Genetics 2001; 60: 220-225
Primary open-angle glaucoma (POAG) is a highly prevalent optic neuropathy and a major cause of irreversible blindness, with elevation of intraocular pressure (IOP) being a primary risk factor. The trabecular meshwork-inducible glucocorticoid response (TIGR)/Myocilin (MYOC) gene coding region is mutated in 3-4% of POAG patients. Here, in a retrospective study of 142 POAG patients, the authors evaluated the influence on glaucoma phenotype of a novel biallelic polymorphism (-1000C/G) located in the upstream region of the MYOC gene. Allele frequencies were similar among patients and controls. However, the G allele (frequency 17.6%), also designated as MYOC. mt1, was associated with an increased IOP (+4.9 mmHg, p = 0.0004) and a more damaged visual field (p = 0.02). Both effects were predominant in females. Moreover, while IOP in MYOC.mt1 noncarriers decreased very markedly to the normal range between diagnosis and inclusion in the study (p = 3 x 10-5 in both males and females), reflecting successful therapy, it decreased less noticeably in MYOC.mt1 + male patients (p = 0.005) and not at all in MYOC.mt1 + female patients. MYOC.mt1 appears therefore to be an indicator of poor IOP control and greater visual field damage in diagnosed POAG patients, potentially due to a lack of response to therapeutic intervention. Its typing might help in the selection of treatment paradigms for the management of POAG patients.
Dr H.J. Garchon, INSERM U25, Hopital Necker, 161 rue de Sevres, 75743 Paris Cedex 15, France. garchon@necker.fr
Classification:
1.2 Population genetics (Part of: 1 General aspects)