June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
Association of Thrombospondin-1 Polymorphism with Predisposition to Chronic Dry Eye
Author Affiliations & Notes
  • Laura Contreras-Ruiz
    Department of Ophthalmology, Boston University School of Medicine, Boston, MA
  • Bruce Turpie
    Department of Ophthalmology, Boston University School of Medicine, Boston, MA
  • Denise Ryan
    U.S. Army Warfighter Refractive Surgery Research Center, Fort Belvoir, VA
  • Rose Sia
    U.S. Army Warfighter Refractive Surgery Research Center, Fort Belvoir, VA
  • Kraig Bower
    The Wilmer Eye Institute, The Johns Hopkins School of Medicine, Baltimore, MD
  • Darlene Dartt
    Schepens Eye Research Inst and Massachusetts Eye and Ear, Department of Ophthalmology Harvard Medical School, Boston, MA
  • Sharmila Masli
    Department of Ophthalmology, Boston University School of Medicine, Boston, MA
  • Footnotes
    Commercial Relationships Laura Contreras-Ruiz, None; Bruce Turpie, None; Denise Ryan, None; Rose Sia, None; Kraig Bower, None; Darlene Dartt, None; Sharmila Masli, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 2036. doi:
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    • Get Citation

      Laura Contreras-Ruiz, Bruce Turpie, Denise Ryan, Rose Sia, Kraig Bower, Darlene Dartt, Sharmila Masli; Association of Thrombospondin-1 Polymorphism with Predisposition to Chronic Dry Eye. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2036.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: Thrombospondin-1 (TSP-1) is a matricellular protein with immunomodulatory properties. Our previous work showed that TSP-1 deficient mice develop ocular surface inflammation. The purpose was to determine if polymorphism in TSP-1 gene (THBS-1) correlates with the development of the chronic ocular surface inflammatory conditions of dry eye that develops after refractive surgery.

Methods: Genomic DNA and RNA were obtained from conjunctival impression cytology samples of 75 patients before and 3 months after refractive surgery. The samples were assigned to 2 groups: patients with post surgery dry eye (n=59) or healthy controls (n=16). Five TSP-1 single nucleotide polymorphisms (SNPs) were assessed using Sequenom iPLEX Gold platform: SNP1 (rs2228262) A>G, SNP2 (rs2228261) C>T, SNP3 (rs229305) A>G, SNP4 (rs1478604) T>C and SNP5 (rs3743125) G>A. Their association with the development of dry eye was analyzed with gPLINK software and Fisher’s exact test. In addition, expression of TSP-1, and IL-1β (inflammatory marker associated with dry eye) were quantified by RT-PCR on both dry eye and control samples.

Results: Frequencies of TT or CT genotypes (T allele carriers) of SNP2, as well as the GG or GA genotypes (G allele carriers) of SNP3, were 39% in dry eye patients compared to 25% in controls (p = 0.048, odds ratio [OR] 1.9, 95% confidence interval (95% CI) 1.1-3.5). The G allele of SNP1 was detected in 19% of subjects in both groups (p = 1.0, OR 1.0, 95% CI 05 - 2.0). The frequency of SNP4 C allele carriers in dry eye patients was 63% as against 44% in control group (p = 0.003, OR 2.5, 95% CI 1.4 - 4.5). The SNP5 was excluded from analysis due to departure from Hardy-Weinberg equilibrium. Allelic association analysis indicated significant association between SNP4 and development of dry eye (p=0.03) while remaining SNPs did not show any significant allelic associations. Expression of TSP-1 in SNP4 C allele carriers (CC+CT) compared to normal allele (TT) carriers was significantly reduced, while expression of inflammatory cytokine IL-1β was significantly increased.

Conclusions: Our results indicate a significant association between polymorphism in THBS-1 gene and ocular surface inflammation as seen in dry eye. This study provides the very first evidence of a genetic association in dry eye disease and suggests THBS1 as a susceptibility factor of this ocular condition.

Keywords: 557 inflammation • 539 genetics • 486 cornea: tears/tear film/dry eye  
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