Association of a single nucleotide polymorphism in the TIGR/MYOCILIN gene promoter with the severity of primary open-angle glaucoma

Primary open-angle glaucoma (POAG) is a highly prevalent optic neuropathy a nd a major cause of irreversible blindness, with elevation of intraocular p ressure (IOP) being a primary risk factor. The trabecular meshwork-inducibl e glucocorticoid response (TIGR)/MYOCILIN (MYOC) gene coding region is muta ted in 3-4% of POAG patients. Here, in a retrospective study of 142 POAG pa tients, we evaluated the influence on glaucoma phenotype of a novel biallel ic 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 wi th an increased IOP ( + 4.9 mmHg, p = 0.0004) and a more damaged visual fie ld (p = 0.02). Both effects were predominant in females. Moreover, whereas IOP in MYOC.mt1 noncarriers decreased very markedly to the normal range bet ween diagnosis and inclusion in the study (p 3 x 10(-5) in both males and f emales), reflecting successful therapy, it decreased less noticeably in MYO C.mt1 + male patients (p = 0.005) and not at all in MYOC.mt1 + female patie nts. 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 th e selection of treatment paradigms for the management of POAG patients.