Wang Ben-gang, Lv Zhi, Xu Qian, Liu Yong-feng
Organ Transplantation Department of General Surgery Institute, the First Affiliated Hospital of China Medical University, Shenyang 110001, China.
Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Affiliated Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang 110001, China.
Yi Chuan. 2017 Jan 20;39(1):22-31. doi: 10.16288/j.yczz.16-295.
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 MassARRAY 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.
与单个单核苷酸多态性（SNP）相比，单核苷酸多态性之间的基因间相互作用在预测移植排斥风险方面可能具有更好的效能。在本研究中，我们探讨了核苷酸切除修复（NER）基因中SNP之间相互作用的预警功能。通过Sequenom MassARRAY平台对8个NER基因中的38个多态性进行了基因分型，包括XPA、XPC、DDB2、XPB（ERCC3）、XPD（ERCC2）、ERCC1、XPF（ERCC4）和XPG（ERCC5）。单倍型分析表明，XPA rs3176629-rs2808668 C-T以及ERCC5的G-C-C-T和G-C-T-C（优势比分别为1.81、7.72和3.46）增加了移植排斥风险；而ERCC5 rs2094258-rs751402-rs2296147-rs1047768 A-C-T-T降低了风险（优势比=0.35）。多元逻辑回归和多因素降维（DMR）分析一致显示，ERCC2 rs50871、ERCC5 rs1047768和XPC rs2228001 SNP之间存在基因间相互作用，影响移植排斥风险。综上所述，XPC rs2228001、ERCC2 rs50871和ERCC5 rs1047768 SNP之间的相互作用与移植排斥风险相关。
