Heme Oxygenase-1 Genotype of the Donor Is Associated With Graft Survival After Liver Transplantation |
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Authors: | C. I. Buis G. van der Steege D. S. Visser I. M. Nolte B. G. Hepkema M. Nijsten M. J. H. Slooff R. J. Porte |
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Affiliation: | Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery;, Surgical Research Laboratory;, Medical Biology;, Transplantation Immunology;and Surgical Intensive Care Unit, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands |
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Abstract: | Heme oxygenase-1 (HO-1) has been suggested as a cytoprotective gene during liver transplantation. Inducibility of HO-1 is modulated by a (GT)n polymorphism and a single nucleotide polymorphism (SNP) A(-413)T in the promoter. Both a short (GT) n allele and the A-allele have been associated with increased HO-1 promoter activity. In 308 liver transplantations, we assessed donor HO-1 genotype and correlated this with outcome variables. For (GT) n genotype, livers were divided into two classes: short alleles (<25 repeats; class S) and long alleles (≥25 repeats; class L). In a subset, hepatic messenger ribonucleic acid (mRNA) expression was correlated with genotypes. Graft survival at 1 year was significantly better for A-allele genotype compared to TT-genotype (84% vs. 63%, p = 0.004). Graft loss due to primary dysfunction (PDF) occurred more frequently in TT-genotype compared to A-receivers (p = 0.03). Recipients of a liver with TT-genotype had significantly higher serum transaminases after transplantation and hepatic HO-1 mRNA levels were significantly lower compared to the A-allele livers (p = 0.03). No differences were found for any outcome variable between class S and LL-variant of the (GT) n polymorphism. Haplotype analysis confirmed dominance of the A(-413)T SNP over the (GT) n polymorphism. In conclusion, HO-1 genotype is associated with outcome after liver transplantation. These findings suggest that HO-1 mediates graft survival after liver transplantation. |
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Keywords: | Heme oxygenase-1 liver transplantation polymorphism primary dysfunction |
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