title: OPTN gene: profile of patients with glaucoma from India.
abstract: OBJECTIVE
  Optineurin gene (OPTN) mutations are reported in primary open angle glaucoma patients (POAG) from different populations. The coding and noncoding regions of OPTN were screened for mutations in 100 Indian high tension glaucoma patients (HTG). The frequency of the OPTN M98K mutation in an additional 120 patients (70 HTG and 50 normal tension glaucoma [NTG]) was analyzed by restriction enzyme digestion.
  
  
  METHODS
  The HTG patients (about 40 years of age) were characterized by open angles on gonioscopy, with raised intraocular pressure (IOP) more than 21 mmHg (<21 mmHg on office diurnal phasing for NTG), and typical glaucomatous disc changes with corresponding visual field defects in the absence of any secondary cause. One hundred HTG patients and controls were screened for OPTN mutations by direct sequencing using an ABI prism 310/3100 Avant genetic analyzer. The M98K status was analyzed by restriction enzyme digestion with StuI. A genotype/phenotype correlation was also attempted for OPTN sequence alterations with clinical parameters such as age at diagnosis, intraocular pressure, cup:disc ratio, etc. The putative change in the transcription factor binding site for the IVS7 +24G>A polymorphism was attempted with AliBaba software (version 2.1).
  
  
  RESULTS
  Six sequence alterations were observed in the 100 POAG patients by direct sequencing. The M98K substitution was observed in a total of 10 patients (7/170 HTG and 3/50 NTG) contributing to 4.1% in HTG and 6% in the NTG group and not in the controls. The IVS7+24G>A nucleotide change showed a significant difference in the HTG group (7/100) when compared to the control group (0/100) and found to be associated with increased IOP at diagnosis (p=0.03). The IVS7+24G>A polymorphism resulted in the creation of binding sites for transcription factors NF-1 and CPE that were not present in the wild type.
  
  
  CONCLUSIONS
  The current study suggests a possible role of SNPs rather than mutations in OPTN in POAG pathology in the Indian population.
authors.affiliation: Department of Genetics and Molecular Biology, Vision Research Foundation, Sankara Nethralaya, Chennai, Tamil Nadu, India.
authors.forename: S
authors.initials: S
authors.lastname: Sripriya
authors.forename: J
authors.initials: J
authors.lastname: Nirmaladevi
authors.forename: R
authors.initials: R
authors.lastname: George
authors.forename: A
authors.initials: A
authors.lastname: Hemamalini
authors.forename: M
authors.initials: M
authors.lastname: Baskaran
authors.forename: R
authors.initials: R
authors.lastname: Prema
authors.forename: S
authors.initials: S
authors.lastname: Ve Ramesh
authors.forename: T
authors.initials: T
authors.lastname: Karthiyayini
authors.forename: J
authors.initials: J
authors.lastname: Amali
authors.forename: S
authors.initials: S
authors.lastname: Job
authors.forename: L
authors.initials: L
authors.lastname: Vijaya
authors.forename: G
authors.initials: G
authors.lastname: Kumaramanickavel
mesh_terms: D000225:Adenine; D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D044466:Asian People / Q000235:genetics*; D001665:Binding Sites; D018797:Cell Cycle Proteins; D005787:Gene Frequency; D005901:Glaucoma / Q000235:genetics* / Q000503:physiopathology*; D006147:Guanine; D006801:Humans; D007194:India; D007429:Intraocular Pressure; D007438:Introns; D008239:Lysine; D026901:Membrane Transport Proteins; D008715:Methionine; D008875:Middle Aged; D009154:Mutation; D035582:Transcription Factor TFIIIA / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D026901:Membrane Transport Proteins; C409460:OPTN protein, human; D035582:Transcription Factor TFIIIA; D014157:Transcription Factors; D006147:Guanine; D008715:Methionine; D000225:Adenine; D008239:Lysine