Laura Contreras-Ruiz1, Denise S Ryan2, Rose K Sia2, Kraig S Bower3, Darlene A Dartt4, Sharmila Masli5. 1. Department of Ophthalmology, Boston University School of Medicine, Boston, Massachusetts. 2. U.S. Army Warfighter Refractive Surgery Research Center, Fort Belvoir, Virginia. 3. The Wilmer Eye Institute, The Johns Hopkins School of Medicine, Baltimore, Maryland. 4. Schepens Eye Research Institute and Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts. 5. Department of Ophthalmology, Boston University School of Medicine, Boston, Massachusetts. Electronic address: smasli@bu.edu.
Abstract
PURPOSE: 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. DESIGN: Retrospective cohort study. PARTICIPANTS: 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. MAIN OUTCOME MEASURES: 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.
PURPOSE: 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. DESIGN: Retrospective cohort study. PARTICIPANTS: 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. MAIN OUTCOME MEASURES: 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: Clive J Hoggart; Eteban J Parra; Mark D Shriver; Carolina Bonilla; Rick A Kittles; David G Clayton; Paul M McKeigue Journal: Am J Hum Genet Date: 2003-06 Impact factor: 11.025
Authors: Jeffrey I Zwicker; Flora Peyvandi; Roberta Palla; Rossana Lombardi; Maria Teresa Canciani; Andrea Cairo; Diego Ardissino; Luisa Bernardinelli; Kenneth A Bauer; Jack Lawler; Pier Mannucci Journal: Blood Date: 2006-05-09 Impact factor: 22.113
Authors: Dilek Dursun; Min Wang; Dagoberto Monroy; De-Quan Li; Balakrishna L Lokeshwar; Michael E Stern; Stephen C Pflugfelder Journal: Invest Ophthalmol Vis Sci Date: 2002-03 Impact factor: 4.799
Authors: Cintia S De Paiva; Zhuo Chen; Douglas D Koch; M Bowes Hamill; Francis K Manuel; Sohela S Hassan; Kirk R Wilhelmus; Stephen C Pflugfelder Journal: Am J Ophthalmol Date: 2006-03 Impact factor: 5.258
Authors: Jerry Y Niederkorn; Michael E Stern; Stephen C Pflugfelder; Cintia S De Paiva; Rosa M Corrales; Jianping Gao; Karyn Siemasko Journal: J Immunol Date: 2006-04-01 Impact factor: 5.422
Authors: William Foulsham; Thomas H Dohlman; Sharad K Mittal; Yukako Taketani; Rohan Bir Singh; Sharmila Masli; Reza Dana Journal: Ocul Surf Date: 2019-06-05 Impact factor: 5.033
Authors: Marie A Shatos; Robin R Hodges; Masahiro Morinaga; David E McNay; Rakibul Islam; Sumit Bhattacharya; Dayu Li; Bruce Turpie; Helen P Makarenkova; Sharmila Masli; Tor P Utheim; Darlene A Dartt Journal: Exp Eye Res Date: 2016-09-30 Impact factor: 3.467