title: Association of the myocilin mt.1 promoter variant with the worsening of glaucomatous disease over time.
abstract: A major variant of myocilin (MYOC) [TIGR/MYOC mt.1 (-1000 C/G)], present in the gene's promoter, is found to be associated with more rapid progression of the glaucoma disease state. Time-to-event analyses using the Cox proportional hazards model produced substantial statistical evidence that this TIGR/MYOC mt.1(+) variant accelerates worsening for both optic disc and visual field measures of disease progression. These analyses were based on evaluations of 147 patients with primary open-angle glaucoma (POAG) over 35 years of age with an average follow-up of approximately 15 years. Our analyses showed that there are independent effects of the variant on disease progression, taking into account other relevant disease-related baseline risk factors, including age, family history, initial drug treatment, initial surgical treatment, diabetes, gender, myopia, and initial disease severity. The finding that a TIGR/MYOC mt.1(+) determination provided a strong marker for glaucoma progression, above and beyond the other baseline risk factors, suggests a clinical utility in testing for this promoter genotype.
authors.affiliation: Cellular Pharmacology, Department of Ophthalmology, University of California, San Francisco, CA 94143, USA. rpj9027@itsa.ucsf.edu
authors.forename: J R
authors.initials: JR
authors.lastname: Polansky
authors.forename: R P
authors.initials: RP
authors.lastname: Juster
authors.forename: G L
authors.initials: GL
authors.lastname: Spaeth
mesh_terms: D002908:Chronic Disease; D003598:Cytoskeletal Proteins; D018450:Disease Progression; D005136:Eye Proteins / Q000235:genetics*; D005902:Glaucoma, Open-Angle / Q000235:genetics*; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D007429:Intraocular Pressure; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D013997:Time Factors; D000099179:Myocilin
chemical_list: D003598:Cytoskeletal Proteins; D005136:Eye Proteins; D006023:Glycoproteins; D000099179:Myocilin