慢性肾功能衰竭患者线粒体基因组D-loop区突变研究

Mutations of mitochondrial DNA D-loop region in patients with chronic renal failure

目的通过研究慢性肾功能衰竭(CRF)患者及家系成员中线粒体D-loop区的基因变异情况,探讨其与CRF发病之间可能的联系。方法收集42例CRF患者(CRF组)和95名家系成员(UAPM组),以及随机选取的122例正常人(对照组)的外周血,提取线粒体DNA,通过PCR扩增D-loop区并对产物纯化,然后进行基因测序来检测线粒体基因组D-Loop区域基因变异情况,并进行比较,分析该区域基因变异与CRF发病的可能相关性。结果通过与对照组及标准序列比较,共发现79个核苷酸改变,3个高频变异位点,其中总的碱基突变率在CRF组及UAPM组明显增加,两组与对照组碱基变异率差异均有统计学意义(均P<0.01)。CRF组及UAPM组在D310区线粒体微卫星不稳定(mtMSl)及碱基变异率与对照组比较差异均有统计学意义(均P<0.01)。结论线粒体基因组D-Loop区突变可能与CRF的发生、发展有一定的关系。

Objective To investigate the sequence variations of mitochondrial D-loop region in chronic renal failure patients and family members.Methods Forty two patients with chronic renal failure(CRF group)and95unaffected pedigree members(UAPMgroup)were recruited in the study,and122healthy subjects served as normal controls(NC group).Mitochondrial DNA(mtDNA)was extracted from peripheral blood and the D-loop sequence variations were examined by PCR-based assay.The association between D-Loop gene variations and chronic renal failure was analyzed.Results Compared with normalcontrol,79sequence variants were detected,mtDNA exhibited a high rate of sequence variants in patients with CRF and pedigree members.Among these,three high variations were found and base variation rate in CRF and UAPM groups were significantly higher than that in normal control group(P<0.01).The occurrence of mtMSI at D310in CRF and UAPM groups were higher than that in normal control group(P<0.01).Conclusion Genome mutations in mitochondrial D-Loop may be relate to the development of chronic renal failure.