多NER基因多态的交互作用与移植排斥的发病风险相关

发布时间：2018-08-12 16:17

【摘要】：基因间SNP-SNP的交互作用较单一SNP对于疾病的预警作用可能会达到更优的检测效能。本研究探讨了核苷酸切除修复(NER)系统基因中SNP交互作用对移植排斥反应发病风险的预警作用。通过Sequenom Mass ARRAY平台进行基因分型,对8个NER基因中的38个多态进行了检测,包括XPA、XPC、DDB2、XPB(ERCC3)、XPD(ERCC2)、ERCC1、XPF(ERCC4)和XPG(ERCC5)基因。单体型分析结果显示,XPA rs3176629-rs2808668 C-T单体型以及ERCC5 G-C-C-T和G-C-T-C单体型可以增加移植排斥反应的发病风险(分别为OR=1.81,OR=7.72和OR=3.46),而ERCC5 rs2094258-rs751402-rs2296147-rs1047768 A-C-T-T单体型降低了该风险(OR=0.35)。多因素Logistic回归与多因子降维(MDR)分析均表明,ERCC2 rs50871、ERCC5rs1047768和XPC rs2228001多态对于发生移植排斥反应存在基因间SNP-SNP的交互作用。因此,XPC rs2228001、ERCC2 rs50871、ERCC5 rs1047768三者的交互作用与移植排斥反应的发病风险相关。
[Abstract]:The intergenic interaction of SNP-SNP may be more effective in detecting disease than that of single SNP. The purpose of this study was to investigate the role of SNP interaction in nucleotide excision repair (NER) system in predicting the risk of graft rejection. 38 polymorphisms of 8 NER genes, including XPA-XPC-DDB2XPB (ERCC3) XPD (ERCC2) ERCC1 XPF (ERCC4) and XPG (ERCC5) gene, were genotyped by Sequenom Mass ARRAY platform. The results of haplotype analysis showed that XPA rs3176629-rs2808668 C-T haplotype and ERCC5 G-C-C-T and G-C-T-C haplotypes increased the risk of graft rejection (OR1.81 OR7.72 and OR=3.46, respectively), while ERCC5 rs2094258-rs751402-rs2296147-rs1047768 A-C-T-T haplotype reduced the risk (OR=0.35). Multivariate Logistic regression and multivariate (MDR) analysis showed that ERCC2 rs50871ERCC5rs1047768 and XPC rs2228001 polymorphisms had intergenic SNP-SNP interaction in the occurrence of graft rejection. Therefore, the interaction of ERCC2 rs50871 and ERCC5 rs1047768 in XPC rs2228001 was associated with the risk of graft rejection.
【作者单位】：普通外科研究所暨器官移植科中国医科大学附属一院;普通外科研究所暨肿瘤研究所肿瘤病因与筛查研究室中国医科大学附属一院辽宁省高校肿瘤病因与预防重点实验室;
【基金】：国家自然科学基金项目(编号:31200968)资助~~
【分类号】：R392

【相似文献】