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Association of a single nucleotide polymorphism in the TIGR/MYOCILIN gene promoter with the severity of primary open‐angle glaucoma
Author(s) -
Colomb E,
Nguyen TD,
Béchetoille A,
Dascotte JC,
Valtot F,
Brézin AP,
Berkani M,
Copin B,
Gomez L,
Polansky JR,
Garchon HJ
Publication year - 2001
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1034/j.1399-0004.2001.600308.x
Subject(s) - myocilin , glaucoma , medicine , intraocular pressure , open angle glaucoma , ophthalmology , single nucleotide polymorphism , allele , trabecular meshwork , genotype , gene , genetics , biology
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, we 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, whereas IOP in MYOC.mt1 noncarriers decreased very markedly to the normal range between diagnosis and inclusion in the study (p=3×10 −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.