线粒体DNA D-环区单核苷酸多态性与弥漫大B细胞淋巴瘤的相关性

目的：探讨线粒体DNA（mitochondrial DNA，mtDNA）D-环区的单核苷酸多态性（single nucleotide polymorphisms,SNP）与弥漫大B 细胞淋巴瘤（diffuse large B cell lymphoma，DLBCL）患者癌症风险和预后的关系。方法：选取1991 年7 月至2012 年7 月在河北医科大学第四医院血液科接受治疗的108 例DLBCL患者的血液样本，同期159 例健康成人血液样本作为对照。常规提取DNA，进行PCR扩增和SNP位点基因型分析，通过病例对照研究调查了D-环区SNP风险状况。结果：核苷酸微小等位基因73A/G、263A/G、315C/C插入与DLBCL的风险降低有关，核苷酸微小等位基因200G/A与DLBCL的风险增加有关。评估D-环SNP在DLBCL患者的预测能力，5 个SNP位点通过对数秩检验被确认对DLBCL生存预测存在单因素分析统计学意义，多因素分析确认等位基因16304 为DLBCL预后的独立预测因素，16304C患者的生存期明显短于16304T患者（RR=0.513，95% CI为0.266~0.989；P<0.05）。结论：通过对mtDNA D-环区SNP分析可以帮助确定DLBCL的发生风险及高危预后亚组。

Correlation between D-loop SNPs of mitochondrial DNA and diffuse large B cell lymphoma

Objective: To investigate the correlations between single nucleotide polymorphisms (SNPs) in the D-loop of mitochondrial DNA (mtDNA) and the disease risk as well as the prognosis of diffuse large B cell lymphoma (DLBCL). Methods: Blood samples from 108 DLBCL patients treated at the Department of Hematology of the Fourth Hospital of Heibei Medical University during July,1991 and July 2012 were collected for this study; in addition, blood samples from 159 healthy controls during the same period were also collected. DNA was extracted according to the standard protocols for PCR amplification and SNP locus genotype analyses. The risk of D-loop SNPs was investigated by case-control study. Results: The minor alleles of nucleotides 73A/G, 263A/G, 315C/C insert were associated with a decreased risk for DLBCL. The minor allele of the nucleotides 200G/A was associated with an increased risk for DLBCL.To further evaluate the predictive function of D-loop SNPs in DLBCL patients, five SNP sites were identified by Log-Rank test that with statistically significant prediction value of DLBCL survival in a univariate analysis. In a multivariate analysis, allele 16304 was identified as an independent predictor of DLBCL prognosis. The survival time of DLBCL patients with 16304C was significantly shorter than that of patients with 16304T (RR=0.513, 95% CI=0.266-0.989, P<0.05). Conclusion: The analysis of D-loop SNPs in mtDNA can help identifying the occurrence risks and poor prognosis subtypes of DLBCL.