Publication Abstract Display | Type: Published Abstract | Title: A common polymorphism in the COMT gene confers an increased risk of neuropathic pain in HIV sensory neuropathy. | Authors: Ellis R, Letendre SL, Rosario D, Gelman B, Clifford D, Simpson D, McArthur J, Marra C, McCutchan JA, Grant I, for the CHARTER Group | Year: 2012 | Publication: 2012 American Academy of Neurology | Volume: Issue: Pages: | Abstract:Background: This variant reduces COMT enzymatic activity and is associated with altered pain sensitivity and opioid
requirements.
Design/Methods: Subjects were HIV+ volunteers in CHARTER, a multicenter, prospective study of neurological
disease and antiretroviral therapy (ART). HIV-SN was defined by one or more of the following: bilateral distal leg
reduced vibration or sharp sensation or ankle reflexes. Distal neuropathic pain (DNP) was pain occurring bilaterally in
the legs, feet and toes. Paresthesias and numbness also were assessed. Genotypes were obtained using Affymetrix
Genome-Wide Human SNP Array 6.0. Data were analyzed by logistic regression.
Results: Valid genotype and phenotype data were available for 547 subjects; 323 (59%) had HIV-SN and of these 123
(39%) reported DNP. The minor allele frequency (MAF) in this sample was 0.450 (default global population MAF, 0.364).
Among all subjects, the odds of DNP increased with SNP copy number (1 variant allele, OR 1.7 [1.1, 2.6]; p=0.0156; 2
alleles, OR 2.1 [1.3, 3.5] p=0.0043). However, the SNP was related to DNP only in those with SN (OR for 1 variant
allele, 2.1 [1.3, 3.6]; p=0.0047; 2 alleles, 3.0 [1.5, 5.7]; p=0.0011); subjects without SN showed no significant
relationship (p=0.65). SNP copy number was not related to paresthesias or numbness. Individuals with 1 or 2 copies of
the COMT variant SNP did not differ significantly from those with no copies in HIV-SN prevalence, age, CD4 nadir,
proportion on ART or exposure to d-drugs.
Conclusions: A common polymorphism in the COMT gene altered the phenotype of HIV-SN to increase the likelihood
of DNP. Since previous studies showed differential opioid analgesic requirements by COMT genotype, our findings may
have implications for individualized pharmacogenetic therapy. |
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