Association between a common mitochondrial DNA D-loop polycytosine variant and alteration of mitochondrial copy number in human peripheral blood cells
Association between a common mitochondrial DNA D-loop polycytosine variant and alteration of mitochondrial copy number in human peripheral blood cells
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DOI：
10.1136/jmg.2010.077552
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发表时间：
2010-11-01
影响因子：
4
通讯作者：
Wang, P-W
中科院分区：
文献类型：
--
作者：
Liou, C-W;Lin, T-K;Wang, P-W
线粒体DNA（mtDNA）核苷酸16189位的T-到-C转换可以产生可变长度的多聚胞嘧啶序列（poly-C）。这种道变异与疾病有关。方法对837例健康成人的外周血进行mtDNA D-loop序列测定，并与正常对照组进行比较。检测白细胞线粒体DNA拷贝数、血清氧化硫代巴比妥酸反应物质（TBARS）和抗氧化硫醇水平。结果逐步多元线性回归分析确定了影响mtDNA拷贝数表达的因素，包括TBARS、巯基、年龄、体重指数和mtDNA poly-C变异。携带变异不间断多聚C的受试者显示最低的平均（SD）mtDNA拷贝数（330（178）），而携带变异不间断多聚C的受试者（420（273））与野生型（358（215））相比，拷贝数增加。在调整TBARS、硫醇、年龄和体重指数后，三组之间以及不间断多聚-C与来自间断多聚-C和野生型的复合数据之间的差异保持一致（分别为p=0.001和p=0.011）。注意到mtDNA拷贝数减少的趋势与16180-16195区段内连续胞嘧啶数目增加相关（P趋势
Background A T-to-C transition at mitochondrial DNA (mtDNA) nucleotide position 16189 can generate a variable length polycytosine tract (poly-C). This tract variance has been associated with disease. A suggested pathogenesis is that it interferes with the replication process of mtDNA, which in turn decreases the mtDNA copy number and generates disease.Methods In this study, 837 healthy adults' blood samples were collected and determined for their mtDNA D-loop sequence. The mtDNA copy number in the leucocytes and serum levels of oxidative thiobarbituric acid reactive substance (TBARS) and antioxidative thiols were measured. All subjects were then categorised into three groups: wild type or variant mtDNA with presence of an interrupted/uninterrupted poly-C at 16180-16195 segment.Results A step-wise multiple linear regression analysis identified factors affecting expression of mtDNA copy number including TBARS, thiols, age, body mass index and the mtDNA poly-C variant. Subjects harbouring a variant uninterrupted poly-C showed lowest mean (SD) mtDNA copy number (330 (178)), whereas an increased copy number was noted in subjects harbouring variant, interrupted poly-C (420 (273)) in comparison with wild type (358 (215)). The difference between the three groups and between the uninterrupted poly-C and the composite data from the interrupted poly-C and wild type remained consistent after adjustment for TBARS, thiols, age and body mass index (p=0.001 and p=0.011, respectively). A trend for decreased mtDNA copy number in association with increased number of continuous cytosine within the 16180-16195 segment was noted (P-trend