Nasi Milena, Guaraldi Giovanni, Orlando Gabriella, Durante Caterina, Pinti Marcello, Nemes Elisa, Nardini Giulia, Passarino Giuseppe, Cocchi Marina, Esposito Roberto, Mussini Cristina, Cossarizza Andrea
Department of Biomedical Sciences, University of Modena and Reggio Emilia, Italy.
Clin Infect Dis. 2008 Oct 1;47(7):962-8. doi: 10.1086/591706.
The combination of different point mutations in mitochondrial DNA (mtDNA), which are defined as haplogroups, may cause modification in organelle function and may be involved in several pathologies. We analyzed the distribution of mtDNA polymorphisms in human immunodeficiency virus (HIV)-infected patients with lipodystrophy, a relevant adverse event caused by highly active antiretroviral therapy, and their correlation with metabolic and viroimmunologic parameters.
The frequency of the 9 most common European haplogroups was investigated in 346 white, HIV-infected patients with lipodystrophy. Haplogroups were identified on the basis of classic methods. Statistical analysis was performed with use of 1-way analysis of variance, the chi(2) test, and principal-components analysis.
The distribution of mtDNA haplogroups among patients with lipodystrophy was similar to that among the general European population. We found no differences between patients with different haplogroups with regard to viroimmunologic results (plasma HIV load, CD4(+) T cell count, and nadir CD4(+) T cell count), glucose data (glucose, insulin, C-peptide, and glycosylated hemoglobin concentrations and insulin resistance), lipid data (levels of triglycerides, total cholesterol, high- and low-density lipoproteins, and apolipoprotein A1 and B), acid-base balance parameters (lactate level and anion gap), or anthropometric measures (weight, body mass index, and waist-to-hip ratio). No differences were observed in trunk fat levels, leg-fat ratio (which was determined by dual-energy x-ray absorptiometry), or exposure to different drug classes. Principal-components analysis confirmed that the spatial distribution of patients belonging to a given haplogroup was not influenced by different clinical parameters.
Our study indicates that, in HIV-infected patients with lipodystrophy, mtDNA haplogroups are not related to major metabolic changes or to particular viroimmunologic features.
线粒体DNA(mtDNA)中不同点突变的组合,即单倍群,可能导致细胞器功能改变,并可能与多种疾病相关。我们分析了感染人类免疫缺陷病毒(HIV)并患有脂肪代谢障碍(一种由高效抗逆转录病毒疗法引起的相关不良事件)的患者中mtDNA多态性的分布情况,以及它们与代谢和病毒免疫参数的相关性。
在346名感染HIV且患有脂肪代谢障碍的白人患者中,研究了9种最常见欧洲单倍群的频率。单倍群通过经典方法进行鉴定。使用单因素方差分析、卡方检验和主成分分析进行统计分析。
脂肪代谢障碍患者中mtDNA单倍群的分布与欧洲普通人群相似。我们发现不同单倍群的患者在病毒免疫结果(血浆HIV载量、CD4+T细胞计数和最低CD4+T细胞计数)、血糖数据(血糖、胰岛素、C肽和糖化血红蛋白浓度以及胰岛素抵抗)、脂质数据(甘油三酯、总胆固醇、高密度和低密度脂蛋白以及载脂蛋白A1和B水平)、酸碱平衡参数(乳酸水平和阴离子间隙)或人体测量指标(体重、体重指数和腰臀比)方面没有差异。在躯干脂肪水平、腿部脂肪比例(通过双能X线吸收法测定)或接触不同药物类别方面也未观察到差异。主成分分析证实,属于给定单倍群的患者的空间分布不受不同临床参数的影响。
我们的研究表明,在感染HIV且患有脂肪代谢障碍的患者中,mtDNA单倍群与主要代谢变化或特定病毒免疫特征无关。