Vanderbilt University, Nashville, TN 37232, USA.
J Neurovirol. 2012 Dec;18(6):511-20. doi: 10.1007/s13365-012-0133-y. Epub 2012 Oct 17.
HIV-associated sensory neuropathy remains an important complication of combination antiretroviral therapy and HIV infection. Mitochondrial DNA haplogroups and single nucleotide polymorphisms (SNPs) have previously been associated with symptomatic neuropathy in clinical trial participants. We examined associations between mitochondrial DNA variation and HIV-associated sensory neuropathy in CNS HIV Antiretroviral Therapy Effects Research (CHARTER). CHARTER is a USA-based longitudinal observational study of HIV-infected adults who underwent a structured interview and standardized examination. HIV-associated sensory neuropathy was determined by trained examiners as ≥1 sign (diminished vibratory and sharp-dull discrimination or ankle reflexes) bilaterally. Mitochondrial DNA sequencing was performed and haplogroups were assigned by published algorithms. Multivariable logistic regression of associations between mitochondrial DNA SNPs, haplogroups, and HIV-associated sensory neuropathy were performed. In analyses of associations of each mitochondrial DNA SNP with HIV-associated sensory neuropathy, the two most significant SNPs were at positions A12810G [odds ratio (95 % confidence interval) = 0.27 (0.11-0.65); p = 0.004] and T489C [odds ratio (95 % confidence interval) = 0.41 (0.21-0.80); p = 0.009]. These synonymous changes are known to define African haplogroup L1c and European haplogroup J, respectively. Both haplogroups were associated with decreased prevalence of HIV-associated sensory neuropathy compared with all other haplogroups [odds ratio (95 % confidence interval) = 0.29 (0.12-0.71); p = 0.007 and odds ratio (95 % confidence interval) = 0.42 (0.18-1.0); p = 0.05, respectively]. In conclusion, in this cohort of mostly combination antiretroviral therapy-treated subjects, two common mitochondrial DNA SNPs and their corresponding haplogroups were associated with a markedly decreased prevalence of HIV-associated sensory neuropathy.
HIV 相关感觉神经病变仍然是联合抗逆转录病毒治疗和 HIV 感染的重要并发症。线粒体 DNA 单倍群和单核苷酸多态性 (SNP) 先前与临床试验参与者的症状性神经病有关。我们在中枢神经系统 HIV 抗逆转录病毒治疗效果研究 (CHARTER) 中检查了线粒体 DNA 变异与 HIV 相关感觉神经病变之间的关联。CHARTER 是一项基于美国的纵向观察性研究，涉及接受过结构化访谈和标准化检查的 HIV 感染成年人。HIV 相关感觉神经病变由经过培训的检查人员确定为双侧≥1 个体征（振动觉和锐钝觉辨别力下降或踝反射减弱）。进行线粒体 DNA 测序，并通过已发表的算法分配单倍群。进行多变量逻辑回归分析线粒体 DNA SNP、单倍群与 HIV 相关感觉神经病变之间的关联。在分析每个线粒体 DNA SNP 与 HIV 相关感觉神经病变的关联时，两个最显著的 SNP 位于位置 A12810G[比值比 (95%置信区间) = 0.27 (0.11-0.65)；p = 0.004]和 T489C[比值比 (95%置信区间) = 0.41 (0.21-0.80)；p = 0.009]。这些同义变化分别已知定义为非洲单倍群 L1c 和欧洲单倍群 J。与所有其他单倍群相比，这两个单倍群均与 HIV 相关感觉神经病变的患病率降低相关[比值比 (95%置信区间) = 0.29 (0.12-0.71)；p = 0.007 和比值比 (95%置信区间) = 0.42 (0.18-1.0)；p = 0.05]。总之，在这个主要接受联合抗逆转录病毒治疗的受试者队列中，两个常见的线粒体 DNA SNP 及其相应的单倍群与 HIV 相关感觉神经病变的患病率显著降低相关。
