title: Little evidence for association of the glaucoma gene MYOC with open-angle glaucoma.
abstract: BACKGROUND/AIM To determine if overexpression of the glaucoma gene MYOC is involved in the development of open-angle glaucoma (OAG) and if its promoter variants are associated with glaucoma in the Korean population. METHODS Human trabecular meshwork cells were cultured in the presence of ophthalmic steroids such as fluorometholone, fluorometholone acetate, dexamethasone, prednisolone acetate and rimexolone. The cells were cultured at a hydrostatic pressure of 32 mm Hg above atmospheric pressure and induction of MYOC was evaluated by northern blot analysis. Genomic DNA was extracted from blood samples obtained from 74 normal controls and 168 unrelated Korean patients with OAG, including primary OAG, normal tension glaucoma and steroid-induced glaucoma. A 461 base pair (bp) DNA fragment of the MYOC promoter region was amplified using PCR and its genotype was analysed by directly sequencing the product. RESULTS The potencies of steroid eye drops in MYOC induction in vitro was the same regardless of their potential for elevating intraocular pressure in vivo. Hydrostatic pressure had no effect on MYOC induction. A dinucleotide repeat polymorphism and three single nucleotide polymorphisms were identified, but no obvious differences in the genotype distribution and allele frequency of the variants between the control group and any type of OAG were observed. CONCLUSION Our data suggest that MYOC overexpression is not a cause or an effect of intraocular pressure elevation and that MYOC itself is not associated with OAG.
authors.affiliation: Department of Ophthalmology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, South Korea.
authors.forename: Seongsoo
authors.initials: S
authors.lastname: Sohn
authors.forename: Wonhee
authors.initials: W
authors.lastname: Hur
authors.forename: Young Ran
authors.initials: YR
authors.lastname: Choi
authors.forename: Yun Shin
authors.initials: YS
authors.lastname: Chung
authors.forename: Chang-Seok
authors.initials: CS
authors.lastname: Ki
authors.forename: Changwon
authors.initials: C
authors.lastname: Kee
mesh_terms: D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005902:Glaucoma, Open-Angle / Q000235:genetics*; D005938:Glucocorticoids / Q000494:pharmacology; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D006874:Hydrostatic Pressure; D020641:Polymorphism, Single Nucleotide; D014129:Trabecular Meshwork / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000099179:Myocilin
chemical_list: D003598:Cytoskeletal Proteins; D005136:Eye Proteins; D005938:Glucocorticoids; D006023:Glycoproteins; D000099179:Myocilin
references.citation: Arch Ophthalmol. 2001 Nov;119(11):1674-8
references.pmid: 11709019
references.citation: Invest Ophthalmol Vis Sci. 1998 Mar;39(3):517-25
references.pmid: 9501861
references.citation: J Glaucoma. 2004 Oct;13(5):377-84
references.pmid: 15354075
references.citation: Ophthalmic Res. 2005 Sep-Oct;37(5):235-42
references.pmid: 16020952
references.citation: Br J Ophthalmol. 2000 Sep;84(9):1078
references.pmid: 11032443
references.citation: Clin Genet. 2003 Jul;64(1):18-27
references.pmid: 12791035
references.citation: Arch Ophthalmol. 1996 Aug;114(8):933-7
references.pmid: 8694727
references.citation: Mol Vis. 2007 Jun 14;13:862-72
references.pmid: 17615537
references.citation: Invest Ophthalmol Vis Sci. 2001 Jan;42(1):145-52
references.pmid: 11133859
references.citation: Acta Ophthalmol Scand. 2002 Aug;80(4):384-6
references.pmid: 12190780
references.citation: Mol Cell Biol. 2001 Nov;21(22):7707-13
references.pmid: 11604506
references.citation: Invest Ophthalmol Vis Sci. 2001 Dec;42(13):3165-72
references.pmid: 11726618
references.citation: Arch Ophthalmol. 2002 Sep;120(9):1189-97
references.pmid: 12215093
references.citation: Mol Cell Biol. 2004 Oct;24(20):9019-25
references.pmid: 15456875
references.citation: Eur J Hum Genet. 2005 Mar;13(3):384-7
references.pmid: 15483649
references.citation: Arch Ophthalmol. 1980 Sep;98(9):1577-8
references.pmid: 6893544
references.citation: Invest Ophthalmol Vis Sci. 2002 Jan;43(1):33-40
references.pmid: 11773009
references.citation: Clin Genet. 2001 Sep;60(3):220-5
references.pmid: 11595024
references.citation: Science. 1997 Jan 31;275(5300):668-70
references.pmid: 9005853
references.citation: Mol Vis. 2005 Nov 02;11:916-21
references.pmid: 16280977
references.citation: Invest Ophthalmol Vis Sci. 2000 Jun;41(7):1724-9
references.pmid: 10845592
references.citation: Invest Ophthalmol Vis Sci. 2000 Dec;41(13):4163-8
references.pmid: 11095610
references.citation: Invest Ophthalmol Vis Sci. 2005 Jan;46(1):223-34
references.pmid: 15623777
references.citation: J Biol Chem. 1998 Mar 13;273(11):6341-50
references.pmid: 9497363
references.citation: Ann Ocul (Paris). 1954 Sep;187(9):805-16
references.pmid: 13218439