线粒体 DNA 亚单倍群 L0a2 和 L2a 修饰了马拉维成年人在含司他夫定的高效抗逆转录病毒治疗中发生周围神经病的易感性。
Mitochondrial DNA subhaplogroups L0a2 and L2a modify susceptibility to peripheral neuropathy in malawian adults on stavudine containing highly active antiretroviral therapy.
机构信息
*Division of Human Genetics, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; and †Department of Pathology, ‡Department of Medicine, and §Malawi-Liverpool Wellcome Trust Clinical Research Programme, College of Medicine, University of Malawi, Malawi.
出版信息
J Acquir Immune Defic Syndr. 2013 Aug 15;63(5):647-52. doi: 10.1097/QAI.0b013e3182968ea5.
BACKGROUND
Peripheral neuropathy (PN) is one of the main toxicities associated with stavudine. Genetic variants in mitochondrial DNA (mtDNA) haplogroups have been associated with increased risk of developing PN in European non-Hispanic and black patients on stavudine containing antiretroviral therapy (ART). We investigated mtDNA haplogroups and their role in susceptibility to stavudine-induced peripheral in Malawian patients on ART.
METHOD
Two hundred and fifteen adults on stavudine containing regimens were recruited from the ART clinic at Queen Elizabeth Central Hospital, Blantyre, into a cross-sectional study to investigate the effects of genetic variants in mtDNA of individuals in relation to response to treatment. Patients were categorized according to whether or not they had developed PN after a minimum of 6 months on stavudine containing ART. Whole mtDNA coding regions of each patient were sequenced, and CD4 count, viral load, and creatinine were determined. The mtDNA variation was correlated with clinical characteristics.
RESULTS
Fifty-three (25%) of the participants developed PN after starting stavudine containing ART. Mitochondrial DNA subhaplogroup L0a2 was independently associated with increased risk of PN in a multivariate model (odds ratio, 2.23; 95% confidence interval, 1.14 to 4.39; P = 0.019), and subhaplogroup L2a was independently associated with reduced risk of PN (odds ratio, 0.39; 95% confidence interval, 0.16 to 0.94; P = 0.036).
CONCLUSIONS
Genetic variation in mtDNA confers differential risk of developing PN in patients on stavudine containing ART among Malawians.
背景
周围神经病变（PN）是与司他夫定相关的主要毒性之一。线粒体 DNA（mtDNA）单倍群中的遗传变异与接受包含司他夫定的抗逆转录病毒疗法（ART）的欧洲非裔和黑人患者发生 PN 的风险增加相关。我们研究了 mtDNA 单倍群及其在马拉维接受包含司他夫定的 ART 的患者中对司他夫定诱导的周围神经病变易感性的作用。
方法
从布兰太尔伊丽莎白女王中央医院的 ART 诊所招募了 215 名接受包含司他夫定方案的成年人，进行横断面研究，以调查个体 mtDNA 中的遗传变异与治疗反应之间的关系。根据患者在接受包含司他夫定的 ART 至少 6 个月后是否发生 PN，将患者分为两组。对每位患者的整个 mtDNA 编码区进行测序，并测定 CD4 计数、病毒载量和肌酐。将 mtDNA 变异与临床特征相关联。
结果
53（25%）名参与者在开始接受包含司他夫定的 ART 后出现 PN。在多变量模型中，线粒体 DNA 亚单倍群 L0a2 与 PN 的风险增加独立相关（优势比，2.23；95%置信区间，1.14 至 4.39；P=0.019），亚单倍群 L2a 与 PN 的风险降低独立相关（优势比，0.39；95%置信区间，0.16 至 0.94；P=0.036）。
结论
mtDNA 中的遗传变异赋予了接受包含司他夫定的 ART 的马拉维患者发生 PN 的不同风险。
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