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首页> 外文期刊>AIDS Research and Human Retroviruses >Mitochondrial DNA variation and changes in adiponectin and endothelial function in HIV-infected adults after antiretroviral therapy initiation
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Mitochondrial DNA variation and changes in adiponectin and endothelial function in HIV-infected adults after antiretroviral therapy initiation

机译：抗逆转录病毒疗法启动后，感染艾滋病毒的成年人的线粒体DNA变异以及脂联素和内皮功能的变化

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Studies in persons of European descent have suggested that mitochondrial DNA (mtDNA) haplogroups influence antiretroviral therapy (ART) toxicity. We explored associations between mtDNA variants and changes in endothelial function and biomarkers among non-Hispanic white, ART-naive subjects starting ART. A5152s was a substudy of A5142, a randomized trial of initial class-sparing ART regimens that included efavirenz or lopinavir/ritonavir with nucleoside reverse transcriptase inhibitors (NRTIs), or both without NRTIs. Brachial artery flow-mediated dilation (FMD) and cardiovascular biomarker assessments were performed at baseline and at weeks 4 and 24. Ten haplogroup-defining mtDNA polymorphisms were determined. FMD and biomarker changes from baseline to week 24 by mtDNA variant were assessed using Wilcoxon rank-sum tests. Thirty-nine non-Hispanic white participants had DNA and 24-week data. The nonsynonymous m.10398A>G mtDNA polymorphism (N=8) was associated with higher median baseline adiponectin (5.0 vs. 4.2 μg/ml; p=0.003), greater absolute (-1.9 vs. -0.2 μg/ml) and relative (-33% vs. -3%) adiponectin decreases (p<0.001 for both), and lower week 24 brachial artery FMD (3.6% vs. 5.4%; p=0.04). Individual mtDNA haplogroups, including haplogroups H (N=13) and U (N=6), were not associated with adiponectin or FMD changes. In this small pilot study, adiponectin and brachial artery FMD on ART differed in non-Hispanic whites with a nonsynonymous mtDNA variant associated with several human diseases. These preliminary findings support the hypothesis that mtDNA variation influences metabolic ART effects. Validation studies in larger populations and in different racial/ethnic groups that include m.10398G carriers are needed.
机译：欧洲血统的研究表明，线粒体DNA（mtDNA）单倍体会影响抗逆转录病毒疗法（ART）的毒性。我们探讨了非DNA的白人，初次接受ART的受试者中mtDNA变异与内皮功能和生物标记物变化之间的关联。 A5152s是A5142的子研究，A5142是一项最初的保留ART方案的随机试验，其中包括依法韦仑或洛匹那韦/利托那韦联合核苷类逆转录酶抑制剂（NRTIs），或两者均不含NRTIs。在基线以及第4和24周进行肱动脉血流介导的扩张（FMD）和心血管生物标志物评估。确定了十个定义单倍群的mtDNA多态性。使用Wilcoxon秩和检验评估mtDNA变异从基线到第24周的口蹄疫和生物标志物变化。 39名非西班牙裔白人参与者有DNA和24周数据。非同义的m.10398A> G mtDNA多态性（N = 8）与基线脂联素中位数较高（5.0 vs. 4.2μg/ ml; p = 0.003），绝对值较大（-1.9 vs.-0.2μg/ ml）和相对相关（-33％对-3％）脂联素减少（两者均p <0.001），而第24周肱动脉FMD降低（3.6％对5.4％; p = 0.04）。单个mtDNA单倍群，包括单倍群H（N = 13）和U（N = 6），与脂联素或FMD变化无关。在这项小型先导研究中，非西班牙裔白人的脂联素和肱动脉口蹄疫在非西班牙裔白人中存在差异，其mtDNA变异与人类多种疾病有关。这些初步发现支持了mtDNA变异影响代谢ART效应的假说。需要在更大的人群以及包括m.10398G携带者的不同种族/族裔群体中进行验证研究。

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