title: Polymorphism in THBS1 gene is associated with post-refractive surgery chronic ocular surface inflammation.
abstract: OBJECTIVE
  To determine the association of single nucleotide polymorphisms (SNPs) of the thrombospondin 1 (THBS1) gene with development of chronic ocular surface inflammation (keratoconjunctivitis) after refractive surgery.
  
  
  METHODS
  Retrospective cohort study.
  
  
  METHODS
  Active duty U.S. Army soldiers (n = 143) who opted for refractive surgery.
  
  
  METHODS
  Conjunctival impression cytology samples collected from participants before the surgery were used to harvest DNA for genotyping 5 THBS1 SNPs (rs1478604, rs2228262, rs2292305, rs2228262, and rs3743125) using the Sequenom iPLEX Gold platform (Sequenom, San Diego, CA). Samples collected after surgery were used to harvest RNA for gene expression analysis by real-time polymerase chain reaction (PCR). Participants were followed for 1 year after surgery to monitor the status of keratoconjunctivitis.
  
  
  METHODS
  Genetic basis of the development of chronic keratoconjunctivitis after refractive surgery.
  
  
  RESULTS
  Carriers of minor alleles of 3 SNPs each were found to be more susceptible to developing chronic keratoconjunctivitis (rs1478604: odds ratio [OR], 2.5; 95% confidence interval [CI], 1.41-4.47; P = 2.5 × 10(-3); rs2228262 and rs2292305: OR, 1.9; 95% CI, 1.05-3.51; P = 4.8 × 10(-2)). Carriers of the rs1478604 minor allele expressed significantly reduced levels of thrombospondin 1 (TSP1) (P = 0.042) and increased levels of an inflammatory cytokine associated with keratoconjunctivitis, interleukin-1β (P = 0.025), in their ocular surface epithelial cells compared with homozygous major allele controls.
  
  
  CONCLUSIONS
  Genetic variation in the THBS1 gene that results in decreased expression of the encoded glycoprotein TSP1 in ocular surface epithelial cells significantly increases the susceptibility to develop chronic ocular surface inflammation after refractive surgery. Further investigation of THBS1 SNPs in a larger sample size is warranted.
authors.affiliation: Department of Ophthalmology, Boston University School of Medicine, Boston, Massachusetts.
authors.forename: Laura
authors.initials: L
authors.lastname: Contreras-Ruiz
authors.affiliation: U.S. Army Warfighter Refractive Surgery Research Center, Fort Belvoir, Virginia.
authors.forename: Denise S
authors.initials: DS
authors.lastname: Ryan
authors.affiliation: U.S. Army Warfighter Refractive Surgery Research Center, Fort Belvoir, Virginia.
authors.forename: Rose K
authors.initials: RK
authors.lastname: Sia
authors.affiliation: The Wilmer Eye Institute, The Johns Hopkins School of Medicine, Baltimore, Maryland.
authors.forename: Kraig S
authors.initials: KS
authors.lastname: Bower
authors.affiliation: Schepens Eye Research Institute and Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts.
authors.forename: Darlene A
authors.initials: DA
authors.lastname: Dartt
authors.affiliation: Department of Ophthalmology, Boston University School of Medicine, Boston, Massachusetts. Electronic address: smasli@bu.edu.
authors.forename: Sharmila
authors.initials: S
authors.lastname: Masli
mesh_terms: D000328:Adult; D002908:Chronic Disease; D015331:Cohort Studies; D015352:Dry Eye Syndromes / Q000209:etiology / Q000235:genetics; D005260:Female; D060005:Genotyping Techniques; D006801:Humans; D053583:Interleukin-1beta; D007637:Keratoconjunctivitis / Q000209:etiology / Q000235:genetics*; D020731:Keratomileusis, Laser In Situ; D008297:Male; D008889:Military Personnel; D018903:Photorefractive Keratectomy; D020641:Polymorphism, Single Nucleotide; D011183:Postoperative Complications; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D019700:Thrombospondin 1 / Q000235:genetics*; D059467:Transcriptome; D014481:United States; D055815:Young Adult
chemical_list: D053583:Interleukin-1beta; D019700:Thrombospondin 1