Abstract

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. 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. 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. 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.

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