Polymorphism in THBS1 gene is associated with post-refractive surgery chronic ocular surface inflammation
Open accessAbstract
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.
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Conjunctival specimens from patients with the TSP1 minor CC allele SNP rs1478604 are reported to have lower TSP1 expression than the major allele SNP (TT).
“Conjunctival (CIC) specimens from patients with the TSP1 minor CC allele SNP rs1478604 are reported to have lower TSP1 expression than the major allele SNP (TT) [16].”
From Thrombospondin-1, BIM and CFH polymorphisms and response to anti-VEGF treatment in neovascular age- related macular degeneration patients (2024) · cites this paper as [16]
The Results section reports significantly lower TSP1 expression in CIC samples from rs1478604 minor-allele carriers (CT and CC combined) than from TT individuals. It does not establish a separate CC-versus-TT result; the Discussion notes only that one CC subject had the lowest expression. (LLM, conf=0.88)
Experimental — accuracy not yet measuredTSP1 SNP rs1478604 is linked to decreased TSP1 expression with a subsequent increase in IL1β expression in chronic ocular surface inflammation following refractive surgery.
“TSP1 single nucleotide polymorphism (SNP; rs1478604) is linked to decreased TSP1 expression with a subsequent increase in interleukin 1β (IL1β) expression in chronic ocular surface inflammation following refractive surgery [16]”
From Thrombospondin-1, BIM and CFH polymorphisms and response to anti-VEGF treatment in neovascular age- related macular degeneration patients (2024) · cites this paper as [16]
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OPHTHALMIC ASPECTS OF FIBROMYALGIA
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- Authors
- Contreras-Ruiz, L., Ryan, D. S., Sia, R. K., Bower, K. S., Dartt, D. A., & Masli, S.
- Affiliations
- United States Army (US)
- Johns Hopkins University (US)
- Massachusetts Eye and Ear Infirmary (US)
- Boston University (US)
- Corresponding author
- Masli, Sharmila
- Venue
- Ophthalmology
- Publisher
- Elsevier BV
- Published
- 2014-07
- Volume
- 121
- Issue
- 7
- Pages
- 1389-1397
- ISSN
- 0161-6420 (ISSN-L)
- PMC
- PMC4197802
- OpenAlex
- W2019205435
- Cited by
- 58
- References
- 48
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 9 · 2023: 3 · 2022: 3 · 2021: 4 · 2020: 5 · 2019: 5 · 2018: 3 · 2017: 4 · 2016: 5 · 2015: 6 · 2014: 2
- FWCI
- 5.61
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Ophthalmology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Eye Institute (EY015472)
- U.S. Department of Defense (W81XWH11-1-0477)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Ocular Surface and Contact Lens
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Corneal surgery and disorders
- Health Sciences › Medicine › Ophthalmology › Ocular Infections and Treatments
- Keywords
- thrombospondin-1, single nucleotide polymorphisms, refractive surgery, keratoconjunctivitis, genetic susceptibility, IL-1β, gene expression, military personnel
- MeSH terms
- Adult, Chronic Disease, Female, Humans, Keratoconjunctivitis, Male, Military Personnel, Postoperative Complications, Retrospective Studies, United States, Cohort Studies, Dry Eye Syndromes, Photorefractive Keratectomy, Thrombospondin 1, Polymorphism, Single Nucleotide, Keratomileusis, Laser In Situ, Interleukin-1beta, Young Adult, Transcriptome, Genotyping Techniques, Real-Time Polymerase Chain Reaction
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