title: Thrombospondin-1 polymorphisms influence risk of corneal allograft rejection.
abstract: OBJECTIVE
  We investigated single nucleotide polymorphisms (SNPs) of thrombospondin-1 (TSP-1) on the risk of corneal allograft rejection. The TSP-1 is known to be involved in the immune response of the anterior chamber of the eye, activating TGF-β2, promoting peripheral and systemic tolerance, and counteracting the proangiogenic activity of VEGF.
  
  
  METHODS
  Three tagging SNPs spanning the TSP-1 region (rs1478604, A>G; rs2228261, C>T; and rs2228262, A>G) were genotyped. Association with risk of rejection was investigated in a group of 378 corneal transplant recipients with risk factors for allograft rejection. Transplant recipients had completed 3-year follow-up.
  
  
  RESULTS
  The TSP-1 rs1478604 A SNP was associated significantly with an increased risk of corneal allograft rejection (odds ratio [OR], 1.58; 95% confidence interval [CI], 1.02-2.45; P = 0.04) and there was a trend toward the rs1478604, rs2228261, rs2228262 ACA haplotype increasing risk of rejection.
  
  
  CONCLUSIONS
  The results suggest that TSP-1 rs1478604 AA homozygotes may be at increased risk of corneal transplant rejection, especially if they carry the ACA haplotype.
authors.affiliation: School of Clinical Sciences, Bristol Eye Hospital, Bristol, United Kingdom.
authors.forename: Helen L
authors.initials: HL
authors.lastname: Winton
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Bidwell
authors.forename: W John
authors.initials: WJ
authors.lastname: Armitage
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D064591:Allografts; D003316:Corneal Diseases / Q000601:surgery; D016039:Corneal Transplantation; D004247:DNA / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006084:Graft Rejection / Q000235:genetics* / Q000378:metabolism; D006085:Graft Survival / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D019700:Thrombospondin 1 / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: D019700:Thrombospondin 1; D004247:DNA
keywords: corneal transplantation; single nucleotide polymorphism; thrombospondin-1