Klauke Bärbel, Wirth Andreas, Zittermann Armin, Bohms Birte, Tenderich Gero, Körfer Reiner, Milting Hendrik
Heart- and Diabetescenter NRW, Universitätsklinikum der Ruhr Universität Bochum, Erich and Hanna Klessmann Institut für Kardiovaskuläre Forschung and Entwicklung, Bad Oeynhausen, Germany.
J Heart Lung Transplant. 2008 Jul;27(7):741-5. doi: 10.1016/j.healun.2008.04.001. Epub 2008 May 23.
Survival for heart transplantation (HTx) patients is limited by nephrotoxicity of the calcineurin inhibitors cyclosporine and tacrolimus. To determine whether genetic factors are involved in the development of renal dysfunction under immunosuppressive therapy, we screened various genes for sequence variations.
In a case-control study we analyzed in parallel polymorphisms within the transforming growth factor-beta1 gene (TGF-beta1; L10P, R25P), the multidrug resistance gene MDR 1 (A893T/S) and the CYP3A5 gene (CYP3A5*1/*3 allele). In total, we included 53 cardiac allograft recipients with renal insufficiency (serum creatinine >or=1.8 mg/dl and glomerular filtration rate <50 ml/min/1.73 m(2)) and 53 patients with normal renal function as controls. The controls were matched with patients for age, gender and post-HTx time. The polymorphisms were assessed by denaturing high-performance liquid chromatography (dHPLC) and direct sequencing. We performed univariate and multivariate logistic regression analysis to assess the association between different gene variants and renal dysfunction.
No significant (p > 0.05) relationship was found between the polymorphisms investigated and the susceptibility of renal insufficiency under immunosuppressive therapy.
Our data do not justify genotyping of the investigated single nucleotide polymorphisms (SNPs) to assess the development of renal dysfunction post-HTx.
心脏移植（HTx）患者的生存受到钙调神经磷酸酶抑制剂环孢素和他克莫司肾毒性的限制。为了确定遗传因素是否参与免疫抑制治疗下肾功能障碍的发生，我们筛查了各种基因的序列变异。
在一项病例对照研究中，我们同时分析了转化生长因子-β1基因（TGF-β1；L10P、R25P）、多药耐药基因MDR 1（A893T/S）和CYP3A5基因（CYP3A5*1/*3等位基因）内的多态性。我们总共纳入了53例肾功能不全的心脏移植受者（血清肌酐≥1.8 mg/dl且肾小球滤过率<50 ml/min/1.73 m²）和53例肾功能正常的患者作为对照。对照组在年龄、性别和心脏移植后时间方面与患者匹配。通过变性高效液相色谱（dHPLC）和直接测序评估多态性。我们进行了单变量和多变量逻辑回归分析，以评估不同基因变异与肾功能障碍之间的关联。
在所研究的多态性与免疫抑制治疗下肾功能不全的易感性之间未发现显著（p>0.05）关系。
我们的数据不支持对所研究的单核苷酸多态性（SNP）进行基因分型以评估心脏移植后肾功能障碍的发生情况。
