Catechol-O-methyltransferase polymorphism Val158Met is associated with distal neuropathic pain in HIV-associated sensory neuropathy
| العنوان: | Catechol-O-methyltransferase polymorphism Val158Met is associated with distal neuropathic pain in HIV-associated sensory neuropathy |
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| المؤلفون: | Jennie Xu, Scott Letendre, Anya Umlauf, Donald Franklin, William S. Bush, Joseph H. Atkinson, John R Keltner, Ronald J. Ellis |
| المصدر: | AIDS (London, England), vol 33, iss 10 AIDS |
| بيانات النشر: | Ovid Technologies (Wolters Kluwer Health), 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Genotyping Techniques, Human immunodeficiency virus (HIV), HIV Infections, Neurodegenerative, medicine.disease_cause, Medical and Health Sciences, Methionine, 0302 clinical medicine, Genotype, 2.1 Biological and endogenous factors, Immunology and Allergy, Prospective Studies, 030212 general & internal medicine, Aetiology, Pain Research, Chronic pain, virus diseases, Valine, Single Nucleotide, Middle Aged, Biological Sciences, Infectious Diseases, Neurological, Neuropathic pain, HIV/AIDS, Female, Chronic Pain, Adult, medicine.medical_specialty, Immunology, Single-nucleotide polymorphism, Catechol O-Methyltransferase, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, Pharmacotherapy, Immune system, Clinical Research, Virology, Internal medicine, Genetics, genetic risk factors, medicine, Humans, Genetic Predisposition to Disease, AIDS-Associated Nephropathy, Polymorphism, Peripheral Neuropathy, neuropathic pain, business.industry, Psychology and Cognitive Sciences, Neurosciences, HIV, medicine.disease, United States, 030104 developmental biology, Endocrinology, Amino Acid Substitution, Sensory neuropathy, Neuralgia, business |
| الوصف: | BACKGROUND: 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), Val(158)Met. This variant confers reduced enzymatic activity and results in higher synaptic dopamine levels. Here we examined the role of Val(158)Met as a predictor of DNP in HIV-SN. METHODS: In 1044HIV-infected individuals enrolled in CNS HIV Antiretroviral Therapy Effects Research, an observational study across six US institutions, we characterized the relationship between Val(158)Met 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 nonpainful symptoms of neuropathy (paresthesia and numbness), and 38% were asymptomatic. Compared with asymptomatic HIV-SN, Val(158)Met 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 Val(158)Met and DNP was significant in European and African genetic ancestry. INTERPRETATION: Val(158)Met 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. |
| وصف الملف: | application/pdf |
| تدمد: | 0269-9370 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::050eec76ad9aaaa29894e2cda3ed9809 https://doi.org/10.1097/qad.0000000000002240 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....050eec76ad9aaaa29894e2cda3ed9809 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 02699370 |
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