Association of functional heme oxygenase-1 gene promoter polymorphism with renal transplantation outcomes
Association of functional heme oxygenase-1 gene promoter polymorphism with renal transplantation outcomes
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DOI：
10.1111/j.1600-6143.2006.01726.x
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发表时间：
2007-04-01
影响因子：
8.8
通讯作者：
Maxwell, A. P.
中科院分区：
文献类型：
--
作者：
Courtney, A. E.;McNamee, P. T.;Maxwell, A. P.
血红素氧合酶-1（HO-1）是一种细胞保护分子，在实验移植模型中表达增加与移植物损伤减少相关。HO-1启动子内的功能性二核苷酸重复（GT）（n）多态性调节基因表达;少量重复（S等位基因< 25）增加转录。评估HO-1基因启动子多态性对肾移植结果的作用。对707对（n = 1414）首次死亡供体肾移植（99%为高加索人）的供体/受体对的DNA进行基因分型。供体（风险比0.89，95%CI 0.71-1.11; p = 0.28）或受体（风险比1.19，95%CI 0.95-1.48; p = 0.13）携带S等位基因对移植物存活率没有显著影响。同样，供体和受体基因型均不影响受体存活率（风险比0.89，95% CI 0.67-1.18; p = 0.41，风险比1.22，95% CI 0.93-1.62; p = 0.16）。在包括显著生存因素的多变量分析中，风险比变化很小。基因型不改变急性排斥反应或慢性移植物肾病的发生率。没有证据表明HO-1基因启动子多态性的S等位基因对临床肾移植中移植物或受体存活率有保护作用。
Heme oxygenase-1 (HO-1) is a cytoprotective molecule and increased expression in experimental transplant models correlates with reduced graft injury. A functional dinucleotide repeat (GT)(n) polymorphism, within the HO-1 promoter, regulates gene expression; a short number of repeats (S-allele < 25) increases transcription. The role of this HO-1 gene promoter polymorphism on renal transplant outcomes was assessed. DNA from 707 donor/recipient pairs (n = 1414) of first deceased donor renal transplants (99% Caucasian) was genotyped. Graft survival was not significantly impacted by carriage of an S-allele by the donor (hazard ratio 0.89, 95% CI 0.71-1.11; p = 0.28) or recipient (hazard ratio 1.19, 95% CI 0.95-1.48; p = 0.13). Similarly neither donor nor recipient genotype influenced recipient survival (hazard ratio 0.89, 95% CI 0.67-1.18; p = 0.41, and hazard ratio 1.22, 95% CI 0.93-1.62; p = 0.16). The hazard ratios changed only minimally in multivariate analysis including significant survival factors. Genotype did not alter the incidence of acute rejection or chronic allograft nephropathy. There is no evidence of a protective effect for the S-allele of the HO-1 gene promoter polymorphism on graft or recipient survival in clinical renal transplantation.