Analysis of the mitochondrial DNA genome in the peripheral blood leukocytes of HIV-infected patients with or without lipoatrophy
Analysis of the mitochondrial DNA genome in the peripheral blood leukocytes of HIV-infected patients with or without lipoatrophy
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DOI：
10.1097/00002030-200203080-00001
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发表时间：
2002-03-08
期刊：
影响因子：
3.8
通讯作者：
Wong, LJ
中科院分区：
文献类型：
--
作者：
McComsey, G;Tan, DJ;Wong, LJ
目的：研究核苷类似物逆转录酶抑制剂（NRTI）相关的线粒体功能障碍的分子机制。方法：外周血样本收集自10名健康人，10名HIV感染者，NRTI治疗的脂肪萎缩患者，和4名HIV感染者初治所有抗逆转录病毒药物。从白细胞和线粒体基因组中分离出DNA，分析DNA缺失，缺失和点mutation.Results：我们不能检测到线粒体DNA（mtDNA）的耗尽，缺失，或DNA重排的任何标本，包括一个从患者暴发性乳酸酸中毒。时间温度梯度凝胶电泳的完整的线粒体基因组的分析揭示了几个HIV感染patients.Conclusion的血液mtDNA的核苷酸替换：我们没有发现任何证据NRTI相关的mtDNA耗竭或总mtDNA突变的HIV感染患者的白细胞，无论他们的治疗史。因此，NRTI诱导的mtDNA突变是组织特异性的，或者HIV疾病中预先存在的mtDNA变异易导致NRTI治疗期间临床上明显的线粒体功能障碍。mtDNA变异在HIV感染者中是否有NRTI治疗的相关临床症状的发展中的意义有待进一步研究。(C)2002年利平科特威廉姆斯威尔金斯。
Objective: To investigate the molecular mechanisms of nucleoside analogue reverse transcriptase inhibitor (NRTI)-associated mitochondrial dysfunction.Methods: Peripheral blood samples were collected from 10 healthy individuals, 10 HIV-infected, NRTI-treated patients with lipoatrophy, and four HIV-infected patients naive to all antiretrovirals. DNA was isolated from the leukocytes and the mitochondrial genome analyzed for DNA depletion, deletions and point mutations.Results: We were not able to detect mitochodrial DNA (mtDNA) depletion, deletions, or DNA rearrangements in any of the specimens, including one from a patient with fulminant lactic acidosis. A complete analysis of the entire mitochondrial genome by temporal temperature gradient gel electrophoresis revealed several nucleotide substitutions in blood mtDNA of several HIV infected patients.Conclusion: We found no evidence for NRTI-associated mtDNA depletion or gross mtDNA mutations in leukocytes of HIV-infected patients, regardless of their treatment history. Thus, either NRTI-induced mutations in mtDNA are tissue-specific or alternatively, pre-existent mtDNA variations in HIV disease predispose to the development of clinically apparent mitochondrial dysfunction during NRTI therapy. The significance of mtDNA variations in the development of mitochondrial-related clinical conditions in HIV patients with or without NRTI therapy is to be further investigated. (C) 2002 Lippincott Williams Wilkins.