title: Variants in optineurin gene and their association with tumor necrosis factor-alpha polymorphisms in Japanese patients with glaucoma.
abstract: OBJECTIVE
  To investigate sequence variations in the optineurin (OPTN) gene and their association with TNF-alpha polymorphisms in Japanese patients with glaucoma.
  
  
  METHODS
  The OPTN gene was analyzed in blood samples from 629 Japanese subjects. There were 194 patients with primary open-angle glaucoma (POAG), 217 with normal-tension glaucoma (NTG), and 218 with no eye disease (control subjects). The gene was screened for mutations by denaturing high-performance liquid chromatography. Genotyping of three polymorphisms of -308G-->A, -857C-->T, and -863C-->A in the TNF-alpha promoter region was performed. The associations between the genotypes and age, intraocular pressure (IOP), and visual field defects at the time of diagnosis were examined.
  
  
  RESULTS
  A possible glaucoma-causing mutation, His26Asp, was identified in 1 of the 411 Japanese patients with glaucoma. A c.412G-->A (Thr34Thr) polymorphism in the OPTN gene was significantly associated with POAG (genotype frequency, P = 0.011; allele frequency, P = 0.003). The frequency of TNF-alpha/-857T and optineurin/412A carriers was significantly higher (P = 0.006) in patients with POAG than in control subjects. Among the patients with POAG who were carriers of TNF-alpha/-857T, the optineurin/412A carriers had significantly worse (P = 0.020) visual field scores than the non-optineurin/412A ones. The frequency of TNF-alpha/-863A and optineurin/603A (or Lys98) carriers was significantly higher in patients with POAG (P = 0.008) or NTG (P = 0.027) than in control subjects. Among the patients with POAG who were carriers of TNF-alpha/-863A, the ones with optineurin/603A (or Lys98) had significantly worse (P = 0.026) visual field scores than did those with non-optineurin/603A (or Lys98).
  
  
  CONCLUSIONS
  These findings demonstrated that the OPTN gene is associated with POAG rather than NTG in the Japanese. Statistical analysis showed a possible interaction between polymorphisms in the OPTN and the TNF-alpha genes that would increase the risk for glaucoma.
authors.affiliation: Department of Ophthalmology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Tomoyo
authors.initials: T
authors.lastname: Funayama
authors.forename: Karin
authors.initials: K
authors.lastname: Ishikawa
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Ohtake
authors.forename: Tomihiko
authors.initials: T
authors.lastname: Tanino
authors.forename: Daijiro
authors.initials: D
authors.lastname: Kurosaka
authors.forename: Itaru
authors.initials: I
authors.lastname: Kimura
authors.forename: Kotaro
authors.initials: K
authors.lastname: Suzuki
authors.forename: Hidenao
authors.initials: H
authors.lastname: Ideta
authors.forename: Kenji
authors.initials: K
authors.lastname: Nakamoto
authors.forename: Noriko
authors.initials: N
authors.lastname: Yasuda
authors.forename: Takuro
authors.initials: T
authors.lastname: Fujimaki
authors.forename: Akira
authors.initials: A
authors.lastname: Murakami
authors.forename: Ryo
authors.initials: R
authors.lastname: Asaoka
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Hotta
authors.forename: Hidenobu
authors.initials: H
authors.lastname: Tanihara
authors.forename: Takashi
authors.initials: T
authors.lastname: Kanamoto
authors.forename: Hiromu
authors.initials: H
authors.lastname: Mishima
authors.forename: Takeo
authors.initials: T
authors.lastname: Fukuchi
authors.forename: Haruki
authors.initials: H
authors.lastname: Abe
authors.forename: Takeshi
authors.initials: T
authors.lastname: Iwata
authors.forename: Naoki
authors.initials: N
authors.lastname: Shimada
authors.forename: Jun
authors.initials: J
authors.lastname: Kudoh
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Shimizu
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Mashima
mesh_terms: D000328:Adult; D000375:Aging; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D001224:Aspartic Acid; D018797:Cell Cycle Proteins; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D005902:Glaucoma, Open-Angle / Q000235:genetics* / Q000503:physiopathology; D006579:Heterozygote; D006639:Histidine; D006801:Humans; D007429:Intraocular Pressure; D008297:Male; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009154:Mutation; D011110:Polymorphism, Genetic; D013912:Threonine; D035582:Transcription Factor TFIIIA / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D014794:Visual Fields
chemical_list: D018797:Cell Cycle Proteins; D026901:Membrane Transport Proteins; C409460:OPTN protein, human; D035582:Transcription Factor TFIIIA; D014409:Tumor Necrosis Factor-alpha; D013912:Threonine; D001224:Aspartic Acid; D006639:Histidine