应用全基因组拷贝数变异方法探索参芪膜肾方治疗特发膜性肾病基因水平机制的研究

摘要

目的：探索特发膜性肾病患者全基因组拷贝数变异与参芪膜肾方疗效的关系。方法：选取80例经参芪膜肾方或经典的激素联合环磷酰胺方案治疗后完全缓解和无效的IMN病例,分为中药有效组(36例)、中药无效组(11例)、西药有效组(18例)和西药无效组(15例)。提取外周血基因组DNA并应用Affymetrix Genome-Wide Human SNP Array 6.0芯片检测全基因组基因拷贝数,应用CNVhac软件进行拷贝数变异( CNV)分析。结果：中药有效组与中药无效组在第5、第6及第8染色体上检测到的CNVs差异具有统计学意义(P<0.05)。其中位于6号染色体上的HLA族基因在中药有效组多数病例中表现为拷贝数扩增,而中药无效组的多数病例则表现为拷贝数缺失。西药有效组与西药无效组之间未检测到具有统计学差异的CNVs。结论：基因背景差异可能是导致参芪膜肾方取得不同疗效的基因水平机制,HLA的同族基因拷贝数变异影响参芪膜肾方疗效的发挥,前者有望成为该方治疗IMN的疗效预测因子,值得进一步深入研究。%Objective:To explore the correlation between Genome Copy Number Variation ( CNV) of the patients of idio-pathic membranous nephropathy (IMN) and the clinical response of ShenQi MoShen Recipe (SQMSR). Methods:Eighty patients were divided into four groups according to the treatment and outcomes:the complete remission ( CR) group of SQMSR was indicated as the TCR group (36 cases);the no remission (NR) group of SQMSR as the TNR group (11 cases);the CR group of the immuno-suppressive agent (IA) as the ICR group (18 cases);the NR group of IA as the INR group (15 cases). Genomic DNA from periph-eral blood was extracted and genotyped with the Affymetrix Genenome-Wide Human SNP Array 6. 0. CNV analysis was performed on the raw data by the software of CNVhac. Results:The most significant CNVs regions among groups were located on chromosome 5, 6 and 8, on which patients of TCR group showed no loss while patients of TNR group showed loss (P<0. 05). The CNV of HLA gene family which located on chromosome 6 showed amplification on patients of TCR group, but loss on patients of TNR group. However, there were no significant CNVs between ICR and INR group. Conclusion:The differences in genetic background of IMN patients might be the cause of different clinical response of SQMSR. The CNVs of HLA gene family could become the predictive factor of the treat-ment of SQMSR and be worthy of further study.