Buis C I, van der Steege G, Visser D S, Nolte I M, Hepkema B G, Nijsten M, Slooff M J H, Porte R J
Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Am J Transplant. 2008 Feb;8(2):377-85. doi: 10.1111/j.1600-6143.2007.02048.x. Epub 2007 Dec 18.
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 (> or =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.
血红素加氧酶-1（HO-1）被认为是肝移植过程中的一种细胞保护基因。HO-1的诱导性受启动子中（GT）（n）多态性和单核苷酸多态性（SNP）A（-413）T的调节。短（GT）（n）等位基因和A等位基因均与HO-1启动子活性增加有关。在308例肝移植中，我们评估了供体HO-1基因型，并将其与结果变量相关联。对于（GT）（n）基因型，肝脏被分为两类：短等位基因（<25个重复序列；S类）和长等位基因（≥25个重复序列；L类）。在一个亚组中，肝脏信使核糖核酸（mRNA）表达与基因型相关。与TT基因型相比，A等位基因基因型的1年移植物存活率显著更高（84%对63%，p = 0.004）。与A受体相比，TT基因型因原发性功能障碍（PDF）导致的移植物丢失更频繁（p = 0.03）。TT基因型肝脏受体移植后血清转氨酶显著更高，且肝脏HO-1 mRNA水平与A等位基因肝脏相比显著更低（p = 0.03）。在（GT）（n）多态性的S类和LL变体之间，未发现任何结果变量存在差异。单倍型分析证实A（-413）T SNP比（GT）（n）多态性更具优势。总之，HO-1基因型与肝移植后的结果相关。这些发现表明HO-1介导肝移植后的移植物存活。
