title: SNPs and interaction analyses of noelin 2, myocilin, and optineurin genes in Japanese patients with open-angle glaucoma.
abstract: OBJECTIVE
  To evaluate the noelin 2 gene as a disease-causing factor for open-angle glaucoma (OAG) and the interactions between the noelin 2 (OLFM2), optineurin (OPTN), and myocilin (MYOC) genes.
  
  
  METHODS
  OLFM2 was analyzed in 770 Japanese subjects including 215 patients with elevated intraocular pressure (IOP), 277 with normal IOP, 38 with juvenile open-angle glaucoma, and 240 control subjects. Two single-nucleotide polymorphisms (SNPs) in OPTN (c.412G-->A and c.603T-->A) and one SNP in MYOC (c.227G-->A) were examined. Single genes were investigated by univariate analysis and the gene-gene interactions by logistic regression analysis. Associations between genotypes and clinical characteristics at the time of diagnosis were examined.
  
  
  RESULTS
  In OLFM2, 12 sequence variants were identified in 770 Japanese subjects. Arg144Gln (exon 4) was identified in two (0.3%) of the patients and in none of the control subjects. Combinations of OLFM2/317A and OPTN/412A or OLFM2/1281T and OPTN/412A were associated with patients with elevated IOP (P = 0.018 or P = 0.012, respectively). The combination of OLFM2/317G and OPTN/603A was significantly associated with elevated IOP (P = 0.018). No significant association was detected between SNPs in OLFM2 and in MYOC. Patients with normal IOP and with OLFM2/678A+OPTN/412G or OLFM2/1281C+OPTN/412G had significantly worse visual field scores (P = 0.022 or 0.030, respectively).
  
  
  CONCLUSIONS
  The Arg144Gln mutation in OLFM2 is a possible disease-causing mutation in Japanese patients with OAG. Common polymorphisms in OLFM2 and OPTN may interactively contribute to the development of OAG, indicating a polygenic etiology.
authors.affiliation: Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Tomoyo
authors.initials: T
authors.lastname: Funayama
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Mashima
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Ohtake
authors.forename: Karin
authors.initials: K
authors.lastname: Ishikawa
authors.forename: Nobuo
authors.initials: N
authors.lastname: Fuse
authors.forename: Noriko
authors.initials: N
authors.lastname: Yasuda
authors.forename: Takeo
authors.initials: T
authors.lastname: Fukuchi
authors.forename: Akira
authors.initials: A
authors.lastname: Murakami
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Hotta
authors.forename: Naoki
authors.initials: N
authors.lastname: Shimada
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D018797:Cell Cycle Proteins; D002851:Chromatography, High Pressure Liquid; D003598:Cytoskeletal Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005136:Eye Proteins / Q000235:genetics*; D005838:Genotype; D005902:Glaucoma, Open-Angle / Q000235:genetics*; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D007429:Intraocular Pressure; D007564:Japan; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009154:Mutation; D009798:Ocular Hypertension / Q000235:genetics; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D025941:Protein Interaction Mapping; D035582:Transcription Factor TFIIIA / Q000235:genetics*; D000099179:Myocilin
chemical_list: D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D016326:Extracellular Matrix Proteins; D005136:Eye Proteins; D006023:Glycoproteins; D026901:Membrane Transport Proteins; D035582:Transcription Factor TFIIIA; D000099179:Myocilin; C409460:OPTN protein, human; C081451:olfactomedin