多NER基因多态的交互作用与移植排斥的发病风险相关

Interactions among polymorphisms of NER genes prompt the risk of transplantation rejection

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。

Better efficacy for predicting the risk of transplantation rejection could be achieved by intergenic interactions among single nucleotide polymorphisms（SNPs） compared with one SNP. In this study, we explored the forewarning function of interactions among SNPs in nucleotide excision repair（NER） genes. Thirty-eight polymorphisms in eight NER genes were genotyped by Sequenom Mass ARRAY platform, including XPA, XPC, DDB2, XPB（ERCC3）, XPD（ERCC2）, ERCC1, XPF（ERCC4）, and XPG（ERCC5）. The haplotype analysis suggested that XPA rs3176629-rs2808668 C-T and ERCC5 G-C-C-T and G-C-T-C（OR = 1.81, 7.72 and 3.46, respectively） increased the risk of transplantation rejection; while ERCC5 rs2094258-rs751402-rs2296147-rs1047768 A-C-T-T decreased the risk（OR = 0.35）. Multiple logistic regression and multifactor dimensionality reduction（DMR） analyses consistently revealed intergenic interactions among ERCC2 rs50871, ERCC5 rs1047768, and XPC rs2228001 SNPs for the risk of transplantation rejection. Taken together, the interactions among XPC rs2228001, ERCC2 rs50871 and ERCC5 rs1047768 SNPs were associated with the risk of transplantation rejection.