University of California San Diego, School of Medicine.
Department of Psychiatry, University of California San Diego.
AIDS. 2019 Aug 1;33(10):1575-1582. doi: 10.1097/QAD.0000000000002240.
Many of those aging with HIV suffer from distal neuropathic pain (DNP) due to HIV-associated sensory neuropathy (HIV-SN). Prior studies have linked chronic pain conditions to a variant of the catechol-O-methyltransferase (COMT), ValMet. This variant confers reduced enzymatic activity and results in higher synaptic dopamine levels. Here we examined the role of ValMet as a predictor of DNP in HIV-SN.
In 1044 HIV-infected individuals enrolled in CNS HIV Antiretroviral Therapy Effects Research, an observational study across six US institutions, we characterized the relationship between ValMet and DNP in HIV-SN. Participants underwent neurologic examination and genotyping. Stratification into genetic ancestry groups was employed to eliminate bias due to genetic background.
Of 590 participants with HIV-SN, 38% endorsed DNP, 24% reported nonpainful symptoms of neuropathy (paresthesia and numbness), and 38% were asymptomatic. Compared with asymptomatic HIV-SN, ValMet was associated with 2.3 higher odds of DNP. There were no increased odds of nonpainful symptoms. The association remained significant after controlling for other risk factors for DNP: lifetime diagnosis of depression, older age, ancestry, cumulative exposure to dideoxynucleoside antiretrovirals, diabetes, and nadir CD4. Stratified by genetic ancestry, the association between ValMet and DNP was significant in European and African genetic ancestry.
ValMet may be a genetic marker for susceptibility to DNP in HIV-SN. Our findings support the notion that differences in pain processing mediated by COMT-related dopamine signaling play a role in susceptibility to DNP in HIV-SN. Because prior studies suggest that the COMT allele may influence dose-response relationships with opioid treatment, knowing COMT genotype could influence management.
许多感染艾滋病病毒的老年人因艾滋病相关感觉神经病变（HIV-SN）而患有远端神经病理性疼痛（DNP）。先前的研究将慢性疼痛状况与儿茶酚-O-甲基转移酶（COMT）的变体 ValMet 联系起来。这种变体赋予较低的酶活性，并导致较高的突触多巴胺水平。在这里，我们研究了 ValMet 作为 HIV-SN 中 DNP 的预测因子的作用。
在 CNS HIV 抗逆转录病毒治疗效果研究中，我们对六个美国机构的观察性研究中的 1044 名 HIV 感染者进行了研究，该研究对 ValMet 与 HIV-SN 中的 DNP 之间的关系进行了特征描述。参与者接受了神经学检查和基因分型。采用遗传祖先群体分层消除了遗传背景引起的偏差。
在 590 名患有 HIV-SN 的参与者中，38%的人有 DNP，24%的人报告有非疼痛性神经病变症状（感觉异常和麻木），38%的人无症状。与无症状的 HIV-SN 相比，ValMet 与 DNP 的关联高出 2.3 倍。非疼痛性症状的几率没有增加。在控制 DNP 的其他危险因素（包括终生诊断为抑郁症、年龄较大、遗传背景、叠氮胸苷抗逆转录病毒药物的累积暴露、糖尿病和 CD4 最低点）后，这种关联仍然显著。按遗传祖先分层，ValMet 与 DNP 之间的关联在欧洲和非洲遗传祖先中具有统计学意义。
ValMet 可能是 HIV-SN 中 DNP 易感性的遗传标志物。我们的研究结果支持这样一种观点，即 COMT 相关多巴胺信号介导的疼痛处理差异在 HIV-SN 中 DNP 的易感性中起作用。由于先前的研究表明 COMT 等位基因可能影响阿片类药物治疗的剂量反应关系，因此了解 COMT 基因型可能会影响管理。
