Mitochondrial DNA haplogroups influence lipoatrophy after highly active antiretroviral therapy.
Mitochondrial DNA haplogroups influence lipoatrophy after highly active antiretroviral therapy.
复制标题
DOI：
10.1097/qai.0b013e3181a324d6
复制
发表时间：
2009-06-01
期刊：
影响因子：
--
通讯作者：
O'Brien SJ
中科院分区：
文献类型：
--
作者：
Hendrickson SL;Kingsley LA;Ruiz-Pesini E;Poole JC;Jacobson LP;Palella FJ;Bream JH;Wallace DC;O'Brien SJ
尽管高活性逆转录病毒疗法（HAART）在降低艾滋病毒感染者的艾滋病发病率方面非常有效，但HAART中包含的某些药物可能导致严重的线粒体毒性。最常见的不良事件之一是脂肪萎缩，即作为核苷类逆转录酶抑制剂（NRTIs）的不良反应，面部、手臂、臀部和/或腿部皮下脂肪的减少。脂肪萎缩的临床症状与遗传性线粒体疾病相似，提示宿主线粒体基因型可能在易感性中起作用。我们在多中心艾滋病队列研究（MACS）中分析了接受HAART治疗的hiv感染的欧美患者的线粒体单倍群与脂肪萎缩严重程度之间的关系，发现线粒体单倍群H与脂肪萎缩增加密切相关（手臂：p = 0.007, OR = 1.77, 95% CI = 1.17-2.69，腿部：p = 0.037, OR = 1.54 95% CI = 1.03-2.31，臀部：p = 0.10, OR = 1.41 95% CI = 0.94-2.12）。我们还看到单倍群T对脂肪萎缩的保护具有临界意义（p = 0.05, OR = 0.52, 95% CI = 0.20-1.00）。这些数据表明，线粒体DNA单倍群可能影响nrti患者脂肪萎缩的倾向。
Although highly active retroviral therapy (HAART) has been extremely effective in lowering AIDS incidence among patients infected with HIV, certain drugs included in HAART can cause serious mitochondrial toxicities. One of the most frequent adverse events is lipoatrophy, which is the loss of subcutaneous fat in the face, arms, buttocks and/or legs as an adverse reaction to nucleoside reverse transcriptase inhibitors (NRTIs). The clinical symptoms of lipoatrophy resemble those of inherited mitochondrial diseases, which suggests that host mitochondrial genotype may play a role in susceptibility. We analyzed the association between mitochondrial haplogroup and severity of lipoatrophy in HIV-infected European American patients on HAART in the Multicenter AIDS cohort Study (MACS) and found that mitochondrial haplogroup H was strongly associated with increased atrophy (arms: p = 0.007, OR = 1.77, 95% CI = 1.17–2.69 legs: p = 0.037, OR = 1.54 95% CI = 1.03–2.31, and buttocks: p = 0.10, OR = 1.41 95% CI = 0.94–2.12). We also saw borderline significance for haplogroup T as protective against lipoatrophy (p = 0.05, OR = 0.52, 95% CI = 0.20–1.00). These data suggest that mitochondrial DNA haplogroup may influence the propensity for lipoatrophy in patients receiving NRTIs.