Leukocyte mitochondrial DNA alteration in systemic lupus erythematosus and its relevance to the susceptibility to lupus nephritis.
Leukocyte mitochondrial DNA alteration in systemic lupus erythematosus and its relevance to the susceptibility to lupus nephritis.
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DOI：
10.3390/ijms13078853
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发表时间：
2012
影响因子：
5.6
通讯作者：
Wei YH
中科院分区：
文献类型：
--
作者：
Lee HT;Lin CS;Chen WS;Liao HT;Tsai CY;Wei YH
线粒体 DNA (mtDNA) 改变在系统性红斑狼疮 (SLE) 病理生理学中的作用仍不清楚。我们研究了 85 名 SLE 患者和 45 名正常受试者的 D310 区域序列变异和 mtDNA 拷贝数变化。从外周静脉血的白细胞中提取白细胞DNA和RNA。分别通过定量实时聚合酶链反应（Q-PCR）和基于PCR的直接测序测定白细胞中D310序列变异和mtDNA拷贝数以及mtDNA编码基因的mRNA表达水平。我们发现，与对照组相比，SLE 患者的白细胞 mtDNA 表现出更高的 D310 异质性频率（69.4% vs. 48.9%，p = 0.022）和更多的 D310 变异（2.2 vs. 1.7，p = 0.014）。在正常对照和低、中或高 SLE 疾病活动指数 (SLEDAI) 患者中，观察到 D310 异质性频率不断增加 (p = 0.021)。高SLEDAI组患者的白细胞mtDNA拷贝数往往较低（p = 0.068），特别是那些携带D310异质性mtDNA的患者（p = 0.020）。此外，mtDNA拷贝数与mtDNA编码的ND1（NADH脱氢酶亚基1）（p = 0.041）和ATPase 6（ATP合酶亚基6）（p = 0.030）基因的mRNA水平呈正相关。 D310 变异较多的患者更容易患狼疮性肾炎 (p = 0.035)。综上所述，我们的研究结果表明，mtDNA拷贝数的减少和mtDNA D310异质性的增加与SLE的发生和进展有关，并且mtDNA D310变异较多的患者更容易患狼疮肾炎。
The role of mitochondrial DNA (mtDNA) alterations in the pathophysiology of systemic lupus erythematosus (SLE) remains unclear. We investigated sequence variations in the D310 region and copy number change of mtDNA in 85 SLE patients and 45 normal subjects. Leukocyte DNA and RNA were extracted from leukocytes of the peripheral venous blood. The D310 sequence variations and copy number of mtDNA, and mRNA expression levels of mtDNA-encoded genes in leukocytes were determined by quantitative real-time polymerase chain reaction (Q-PCR) and PCR-based direct sequencing, respectively. We found that leukocyte mtDNA in SLE patients exhibited higher frequency of D310 heteroplasmy (69.4% vs. 48.9%, p = 0.022) and more D310 variants (2.2 vs. 1.7, p = 0.014) than those found in controls. Among normal controls and patients with low, medium or high SLE disease activity index (SLEDAI), an ever-increasing frequency of D310 heteroplasmy was observed (p = 0.021). Leukocyte mtDNA copy number tended to be low in patients of high SLEDAI group (p = 0.068), especially in those harboring mtDNA with D310 heteroplasmy (p = 0.020). Moreover, the mtDNA copy number was positively correlated with the mRNA level of mtDNA-encoded ND1 (NADH dehydrogenase subunit 1) (p = 0.041) and ATPase 6 (ATP synthase subunit 6) (p = 0.030) genes. Patients with more D310 variants were more susceptible to lupus nephritis (p = 0.035). Taken together, our findings suggest that decrease in the mtDNA copy number and increase in D310 heteroplasmy of mtDNA are related to the development and progression of SLE, and that the patients harboring more D310 variants of mtDNA are more susceptible to lupus nephritis.
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影响因子：
2.6
作者：
Houssiau, F. A.;Ginzler, E. M.
通讯作者：
Ginzler, E. M.
影响因子：
3.9
作者：
Lee, HC;Lim, MLR;Wei, YH
通讯作者：
Wei, YH
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影响因子：
13.6
作者：
Fernandez, David;Perl, Andras
通讯作者：
Perl, Andras
影响因子：
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作者：
BOMBARDIER, C;GLADMAN, DD;CHANG, CH
通讯作者：
CHANG, CH
影响因子：
2.6
作者：
Jonsen, A.;Yu, X.;Bengtsson, A. A.
通讯作者：
Bengtsson, A. A.