IngentaConnect Association of a single nucleotide polymorphism in the TIGR/MYOCI...

Authors: Colomb, E¹; Nguyen, TD²; Béchetoille, A³; Dascotte, J-C⁴; Valtot, F⁵; Brézin, AP⁶; Berkani, M⁷; Copin, B¹; Gomez, L¹; Polansky, JR²; Garchon, H-J¹

Source: Clinical Genetics, Volume 60, Number 3, September 2001 , pp. 220-225(6)

Publisher: Blackwell Publishing

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=3×10⁻⁵ 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.

Keywords: genetics; glaucoma; myocilin; ocular hypertension; promoter; single nucleotide polymorphism

Document Type: Research article

DOI: 10.1034/j.1399-0004.2001.600308.x

Affiliations: 1: INSERM U25, Paris, France; 2: Department of Ophthalmology, University of California at San Francisco, CA, USA; 3: Service d'ophtalmologie, CHU Angers, Angers, 4: Service d'ophtalmologie, CHU Lille, Lille, 5: CHNO Quinze-vingts, 6: Service d'ophtalmologie, CHU Cochin, 7: Institut du Glaucome, Hôpital Saint-Joseph, Paris, France

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