title: Association of Toll-like receptor 4 gene polymorphisms with normal tension glaucoma.
abstract: OBJECTIVE
  Toll-like receptor 4 (TLR4) is a transmembrane receptor that mediates immune responses to exogenous and endogenous ligands and interacts with heat shock proteins, which are reportedly involved in normal tension glaucoma (NTG). This study was undertaken to investigate whether TLR4 polymorphisms are associated with NTG.
  
  
  METHODS
  Two hundred fifty Japanese patients with NTG and 318 Japanese healthy control subjects were recruited. Eight single-nucleotide polymorphisms (SNPs) in the TLR4 gene were genotyped, and allelic and phenotypic diversity was assessed between cases and control subjects.
  
  
  RESULTS
  Strong linkage disequilibrium was observed among all SNPs (D' >or= 0.85), which were located in one haplotype block. With respect to allelic diversity, the minor allele of three SNPs (rs10759930, rs1927914, and rs7037117) carried a significantly increased risk of NTG. With regard to genotypic diversity, individuals with the minor allele of six SNPs (rs10759930, rs1927914, rs1927911, rs12377632, rs2149356, and rs7037117) had a 1.47- to 1.65-fold increased risk of NTG. rs7037117, located in the 3'-untranslated region of TLR4, was most strongly associated with NTG, and when incorporated into a haplotype with rs10759930, the strongest association was detected (P = 0.0038, P(c) = 0.0095).
  
  
  CONCLUSIONS
  Multiple SNPs in the TLR4 gene are associated with the risk of NTG. This finding suggests that the ligands and/or cytokines involved in the TLR4 signaling network may be risk factors for the development of NTG.
authors.affiliation: Department of Ophthalmology, Yokohama City University School of Medicine, Yokohama, Kanagawa, Japan.
authors.forename: Etsuko
authors.initials: E
authors.lastname: Shibuya
authors.forename: Akira
authors.initials: A
authors.lastname: Meguro
authors.forename: Masao
authors.initials: M
authors.lastname: Ota
authors.forename: Kenji
authors.initials: K
authors.lastname: Kashiwagi
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Mabuchi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Iijima
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Kawase
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Makoto
authors.initials: M
authors.lastname: Nakamura
authors.forename: Akira
authors.initials: A
authors.lastname: Negi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sagara
authors.forename: Teruo
authors.initials: T
authors.lastname: Nishida
authors.forename: Masaru
authors.initials: M
authors.lastname: Inatani
authors.forename: Hidenobu
authors.initials: H
authors.lastname: Tanihara
authors.forename: Makoto
authors.initials: M
authors.lastname: Aihara
authors.forename: Makoto
authors.initials: M
authors.lastname: Araie
authors.forename: Takeo
authors.initials: T
authors.lastname: Fukuchi
authors.forename: Haruki
authors.initials: H
authors.lastname: Abe
authors.forename: Tomomi
authors.initials: T
authors.lastname: Higashide
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Sugiyama
authors.forename: Takashi
authors.initials: T
authors.lastname: Kanamoto
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kiuchi
authors.forename: Aiko
authors.initials: A
authors.lastname: Iwase
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Ohno
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Inoko
authors.forename: Nobuhisa
authors.initials: N
authors.lastname: Mizuki
mesh_terms: D000328:Adult; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D005902:Glaucoma, Open-Angle / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D051197:Toll-Like Receptor 4 / Q000235:genetics*
chemical_list: C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4