Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China.
PLoS One. 2012;7(6):e38848. doi: 10.1371/journal.pone.0038848. Epub 2012 Jun 18.
Leprosy is a chronic infectious disease caused by Mycobacterium leprae, an unculturable pathogen with an exceptionally eroded genome. The high level of inactivation of gene function in M. leprae, including many genes in its metabolic pathways, has led to a dependence on host energy production and nutritional products. We hypothesized that host cellular powerhouse--the mitochondria--may affect host susceptibility to M. leprae and the onset of clinical leprosy, and this may be reflected by mitochondrial DNA (mtDNA) background and mtDNA copy number.
We analyzed the mtDNA sequence variation of 534 leprosy patients and 850 matched controls from Yunnan Province and classified each subject by haplogroup. mtDNA copy number, taken to be proportional to mtDNA content, was measured in a subset of these subjects (296 patients and 231 controls) and 12 leprosy patients upon diagnosis.
Comparison of matrilineal components of the case and control populations revealed no significant difference. However, measurement of mtDNA copy number showed that lepromatous leprosy patients had a significantly higher mtDNA content than controls (P = 0.008). Past medical treatments had no effect on the alteration of mtDNA copy number.
Our results suggested that mtDNA content, but not haplogroup, affects leprosy and this influence is limited to the clinical subtype of lepromatous leprosy.
麻风病是由麻风分枝杆菌引起的慢性传染病，这种无法培养的病原体基因组严重受损。麻风分枝杆菌的基因功能高度失活，包括其代谢途径中的许多基因，这导致其对宿主的能量产生和营养产物产生依赖。我们假设宿主细胞的能量工厂——线粒体——可能会影响宿主对麻风分枝杆菌的易感性和临床麻风病的发病，这可能反映在线粒体 DNA（mtDNA）背景和 mtDNA 拷贝数上。
我们分析了来自云南省的 534 例麻风病患者和 850 例匹配对照者的 mtDNA 序列变异，并按单倍群对每个受试者进行分类。在这些受试者中的一部分（296 例患者和 231 例对照者）和 12 例诊断时的麻风病患者中测量了 mtDNA 拷贝数，该拷贝数被认为与 mtDNA 含量成正比。
病例和对照人群的母系成分比较没有显著差异。然而，mtDNA 拷贝数的测量表明，瘤型麻风病患者的 mtDNA 含量明显高于对照者（P = 0.008）。既往的医疗治疗对 mtDNA 拷贝数的改变没有影响。
我们的结果表明，mtDNA 含量而不是单倍群影响麻风病，这种影响仅限于瘤型麻风病的临床亚型。
