Publication Abstract Display
Type: Published Manuscript
Title: Catechol-O-methyltransferase polymorphism Val158Met is associated with distal neuropathic pain in HIV-associated sensory neuropathy.
Authors: Xu J, Umlauf A, Letendre S, Franklin D, Bush WS, Atkinson JH, Keltner J, Ellis RJ
Year: 2019
Publication: AIDS (London, England)
Volume: 33 Issue: 10 Pages: 1575-1582
Abstract: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. METHODS: In 1044 HIV-infected individuals enrolled in CHARTER, an observational study across 6 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. FINDINGS: Of 590 participants with HIV-SN, 38% endorsed DNP, 24% reported non-painful symptoms of neuropathy (paresthesia and numbness), and 38% were asymptomatic. Compared to asymptomatic HIV-SN, ValMet was associated with 2.3 higher odds of DNP. There was no increased odds of non-painful 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. INTERPRETATION: 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.

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