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Genetic basis of chronic keratoconjunctivitis after refractive surgery

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  • Genetic basis of chronic keratoconjunctivitis after refractive surgery

    http://www.ncbi.nlm.nih.gov/pubmed/24679443

    Ophthalmology. 2014 Mar 26. pii: S0161-6420(14)00103-1. doi: 10.1016/j.ophtha.2014.01.033. [Epub ahead of print]
    Polymorphism in THBS1 Gene Is Associated with Post-Refractive Surgery Chronic Ocular Surface Inflammation.

    Contreras-Ruiz L1, Ryan DS2, Sia RK2, Bower KS3, Dartt DA4, Masli S5.
    Author information

    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 inocular 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.
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