Polymorphism in THBS1 Gene Is Associated with Post-Refractive Surgery Chronic Ocular Surface Inflammation

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• 作者：Laura Contreras-Ruiz ; PhD<sup>1sup> ; Denise S. Ryan ; MS<sup>2sup> ; Rose K. Sia ; MD<sup>2sup> ; Kraig S. Bower ; MD<sup>3sup> ; Darlene A. Dartt ; PhD<sup>4sup> ; Sharmila Masli ; PhD<sup>1sup><sup> ; sup><sup>smasli@bu.edu" class="auth_mailsup>
• 关键词：AIM ; ancestry-informative marker ; CI ; confidence interval ; CIC ; conjunctival impression cytology ; D ; diopters ; HWE ; Hardy&ndash ; Weinberg equilibrium ; IL ; interleukin ; LD ; linkage disequilibrium ; OR ; odds ratio ; PCR ; polymerase chain reaction ; SNP ; single nucleotide polymorphism ; SSDE ; Sjö ; gren's syndrome dry eye ; TGF-&szlig ; transforming growth factor-beta ; THBS1 ; thrombospondin 1 ; TSP1 ; thrombospondin 1 ; UTR ; untranslated region
• 刊名：Ophthalmology
• 出版年：July 2014
• 年：2014
• 卷：121
• 期：7
• 页码：1389-1397
• 全文大小：801 K

文摘

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.

sSec_2">Design

spara0015">Retrospective cohort study.

sSec_3">Participants

spara0020">Active duty U.S. Army soldiers (n = 143) who opted for refractive surgery.

sSec_4">Methods

spara0025">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.

sSec_5">Main Outcome Measures

spara0030">Genetic basis of the development of chronic keratoconjunctivitis after refractive surgery.

sSec_6">Results

spara0035">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&ndash;4.47; P = 2.5&times;10<sup>&minus;3sup>; rs2228262 and rs2292305: OR, 1.9; 95% CI, 1.05&ndash;3.51; P = 4.8&times;10<sup>&minus;2sup>). 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-1尾 (P = 0.025), in their ocular surface epithelial cells compared with homozygous major allele controls.

sSec_7">Conclusions

spara0040">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.