• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Pharmacogenetics and genomics >Polymorphisms in type I and II inosine monophosphate dehydrogenase genes and association with clinical outcome in patients on mycophenolate mofetil.
【24h】

Polymorphisms in type I and II inosine monophosphate dehydrogenase genes and association with clinical outcome in patients on mycophenolate mofetil.

机译：I和II型肌苷单磷酸脱氢酶基因的多态性与霉酚酸酯治疗的患者的临床结局相关。

获取原文
获取原文并翻译 | 示例
       
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

BACKGROUND: Type I and II inosine monophosphate dehydrogenases (IMPDH) are the targets of mycophenolic acid (MPA), a widely used immunosuppressant. The aims of this study were: to check the presence of controversial polymorphisms in the IMPDH II gene; to look for new ones; and to investigate potential associations between the most frequent SNPs in both IMPDH genes and clinical outcome in renal transplant recipients. METHODS: The DNA and clinical data of 456 patients from two clinical trials were collected. We sequenced the IMPDH II gene in 80 patients and we genotyped the 456 patients' DNA for the IMPDH II rs4974081, rs11706052, 787C>T and the IMPDH I rs2278293 and rs2278294 SNPs, all of which were earlier reported to be potentially involved in MPA treatment related outcome. We investigated the associations of biopsy proven acute rejection (BPAR), leucopenia, cytomegalovirus infections and other infections with these IMPDH polymorphisms, as well as with demographic, biological and treatment data using multivariate analysis. RESULTS: Many IMPDH II variant alleles referenced in Genbank were not detected and no new polymorphisms were identified. In the whole group of 456 patients, the IMPDH I rs2278294 SNP was associated with a lower risk of BPAR and a higher risk of leucopenia over the first year post-transplantation. No other IMPDH I or IMPDH II polymorphism was significantly associated with any clinical outcome. Interestingly, calcineurin inhibitor and MPA exposures below the therapeutic range increased the risk of BPAR. Cytomegalovirus infection was the factor most closely linked with leucopenia, whereas tacrolimus was associated with fewer infections than cyclosporine. CONCLUSION: IMPDH II genotyping may not improve MPA treatment outcome over the first year post-transplantation, in contrast to MPA and calcineurine inhibitor therapeutic drug monitoring and IMPDH I genotyping.
机译：背景：I型和II型肌苷单磷酸脱氢酶（IMPDH）是广泛使用的免疫抑制剂霉酚酸（MPA）的靶标。这项研究的目的是：检查IMPDH II基因中存在争议的多态性。寻找新的;并研究IMPDH基因中最常见的SNP与肾移植接受者的临床结局之间的潜在关联。方法：收集两项临床试验中456例患者的DNA和临床数据。我们对80位患者的IMPDH II基因进行了测序，并对456位患者的DNA进行了基因分型，分别针对IMPDH II rs4974081，rs11706052、787C> T和IMPDH I rs2278293和rs2278294 SNP，据报道，所有这些都可能参与了MPA治疗相关结果。我们调查了活检证明的急性排斥反应（BPAR），白细胞减少症，巨细胞病毒感染和其他感染与这些IMPDH多态性以及人口统计学，生物学和治疗数据的相关性，使用多变量分析。结果：未检测到Genbank中引用的许多IMPDH II变异等位基因，也未发现新的多态性。在整个456名患者中，IMPDH I rs2278294 SNP与移植后第一年的BPAR风险较低和白细胞减少症的风险较高相关。没有其他IMPDH I或IMPDH II多态性与任何临床结果显着相关。有趣的是，钙调神经磷酸酶抑制剂和MPA暴露低于治疗范围会增加BPAR的风险。巨细胞病毒感染是与白细胞减少症最密切相关的因素，而他克莫司的感染少于环孢素。结论：与MPA和钙调神经磷酸酶抑制剂治疗药物监测和IMPDH I基因分型相反，IMPDH II基因分型在移植后的第一年可能不会改善MPA治疗的结果。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号