title: Association of a single nucleotide polymorphism in the TIGR/MYOCILIN gene promoter with the severity of primary open-angle glaucoma.
abstract: 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 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.
authors.affiliation: INSERM U25, Paris, France.
authors.forename: E
authors.initials: E
authors.lastname: Colomb
authors.forename: T D
authors.initials: TD
authors.lastname: Nguyen
authors.forename: A
authors.initials: A
authors.lastname: Béchetoille
authors.forename: J C
authors.initials: JC
authors.lastname: Dascotte
authors.forename: F
authors.initials: F
authors.lastname: Valtot
authors.forename: A P
authors.initials: AP
authors.lastname: Brézin
authors.forename: M
authors.initials: M
authors.lastname: Berkani
authors.forename: B
authors.initials: B
authors.lastname: Copin
authors.forename: L
authors.initials: L
authors.lastname: Gomez
authors.forename: J R
authors.initials: JR
authors.lastname: Polansky
authors.forename: H J
authors.initials: HJ
authors.lastname: Garchon
mesh_terms: D000483:Alleles; D003598:Cytoskeletal Proteins; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005838:Genotype; D005902:Glaucoma, Open-Angle / Q000235:genetics*; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D008297:Male; D010641:Phenotype; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012189:Retrospective Studies; D012737:Sex Factors; D000099179:Myocilin
chemical_list: D003598:Cytoskeletal Proteins; D005136:Eye Proteins; D006023:Glycoproteins; D000099179:Myocilin