Donor heme oxygenase-1 genotype is associated with renal allograft function1

Donor heme oxygenase-1 genotype is associated with renal allograft function1
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供体血红素加氧酶-1 基因型与肾同种异体移植功能相关1

DOI:
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发表时间:
2004
期刊:
影响因子:
6.2
通讯作者:
O. Wagner
O. Wagner
中科院分区:
医学2区
文献类型:
--
作者:
M. Exner;G. Böhmig;M. Schillinger;H. Regele;B. Watschinger;W. Hörl;M. Raith;C. Mannhalter;O. Wagner

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背景资料。血红素氧合酶(HO)同工酶HO-1最近被认为可以保护移植物免受缺血/再灌注和免疫损伤。该酶的诱导性受HO-1基因启动子中(GT)n二核苷酸长度多态的调控。短重复序列(S类)比长重复序列更能上调HO-1的表达。在本研究中,我们调查了肾移植供者启动子多态性对移植后临床结果的影响。方法:研究方法。在这项回顾性研究中,我们招募了101名身体供体肾移植的受者(他们在1998年6月至1999年9月期间接受了移植)。用从冷冻保存的供者脾细胞中提取的基因组DNA来鉴定HO-1基因。结果。50例患者(49.5%)接受了至少一类S等位基因的供者肾脏移植。来自S等位基因携带者的同种异体肾移植受者的1年血肌酐水平(中位数1.46 mg/dL,四分位数范围1.17-1.68 mg/dL)显著低于非S等位基因携带者的受者(中位数1.61 mg/dL,四分位数范围1.38-2.22 mg/dL,P=0.01)。在调整了冷缺血时间、再次移植、供者年龄、移植物功能延迟和人类白细胞抗原不相合等因素后,S等位基因移植A类受者的血肌酐水平是非S等位基因移植受者的0.81倍(95%可信区间:0.70~0.95,P=0.01)。两组患者在移植物功能延迟、同种异体移植排斥反应或免疫性移植物丢失的发生率方面没有显著差异。结论。我们的数据提示HO-1基因启动子多态性对移植肾功能的影响,从而支持了先前的研究,即HO-1诱导在器官移植中具有保护作用。
Background. The heme oxygenase (HO) isoenzyme HO-1 has recently been suggested to protect transplants from ischemia/reperfusion and immunologic injury. Inducibility of this enzyme is modulated by a (GT)n dinucleotide length polymorphism in the HO-1 gene promoter. Short (class S) repeats are associated with greater up-regulation of HO-1 than are long repeats. In the present study we investigated the impact of the promoter polymorphism of kidney allograft donors on clinical outcomes after transplantation. Methods. We enrolled 101 recipients of cadaveric donor kidney allografts (who underwent transplantation between June 1998 and September 1999) in this retrospective study. The HO-1 genotype was assessed using genomic DNA isolated from cryopreserved donor splenocytes. Results. Fifty patients (49.5%) had received a kidney from a donor with at least one class S allele. Recipients of allografts from a class S allele carrier had significantly lower 1-year serum creatinine levels (median 1.46 mg/dL, interquartile range 1.17–1.68 mg/dL) compared with recipients of a non-class S allele donor kidney (median 1.61 mg/dL, interquartile range 1.38–2.22 mg/dL, P =0.01). After adjustment for cold ischemia time, retransplantation, donor age, delayed graft function, and HLA mismatch, recipients of a class S allele transplant had serum creatinine levels 0.81 times (95% confidence interval: 0.70–0.95, P =0.01) those of recipients of a non-class S allele transplant. The two patient groups did not differ significantly with respect to the incidence of delayed graft function, allograft rejection, or immunologic graft loss. Conclusion. Our data suggest an influence of the HO-1 gene promoter polymorphism on kidney allograft function and thus support previous studies indicating a protective effect of HO-1 induction in organ transplantation.
DOI: 10.1097/00007890-200201270-00023
发表时间: 2002-01-27
期刊: TRANSPLANTATION
影响因子: 6.2
作者:
Katori, M;Buelow, R;Kupiec-Weglinski, JW
通讯作者: Kupiec-Weglinski, JW
适应的异种移植物在抗供体抗体和补体存在的情况下存活,这些抗体和补体会加速初始异种移植物的排斥。
DOI: --
发表时间: 1999
期刊: Journal of immunology (Baltimore, Md. : 1950)
影响因子: --
作者:
Lin,Y;Soares,MP;Sato,K;Takigami,K;Csizmadia,E;Smith,N;Bach,FH
通讯作者: Bach,FH
DOI: 10.1172/jci119634
发表时间: 1997-09-01
影响因子: 15.9
作者:
Ishikawa, K;Navab, M;Lusis, AJ
通讯作者: Lusis, AJ
DOI: 10.1126/science.3029864
发表时间: 1987-02-27
期刊: SCIENCE
影响因子: 56.9
作者:
STOCKER, R;YAMAMOTO, Y;AMES, BN
通讯作者: AMES, BN