Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
PLoS One. 2014 Aug 21;9(8):e103123. doi: 10.1371/journal.pone.0103123. eCollection 2014.

Genetic Variation in Iron Metabolism Is Associated with Neuropathic Pain and Pain Severity in HIV-Infected Patients on Antiretroviral Therapy.

Author information

  • 1Department of Genomic Medicine, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio, United States of America; Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio, United States of America.
  • 2Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
  • 3Department of Neurology, University of California San Diego, San Diego, California, United States of America.
  • 4Scripps Genomic Medicine, Scripps Translational Science Institute, and Scripps Health, La Jolla, California, United States of America.
  • 5Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
  • 6Department of Neurology, University of Washington, Seattle, Washington, United States of America.
  • 7Department of Neurology, Icahn School of Medicine of Mt. Sinai, New York, New York, United States of America.
  • 8Department of Neurology, Johns Hopkins University, Baltimore, Maryland, United States of America.
  • 9Department of Neurology, Washington University, St. Louis, Missouri, United States of America.
  • 10Department of Medicine, University of Washington, Seattle, Washington, United States of America.
  • 11Department of Pathology, University of Texas Medical Branch, Galveston, Texas, United States of America.
  • 12Department of Medicine, University of California San Diego, San Diego, California, United States of America.
  • 13HIV Neurobehavioral Research Center & CHARTER Center, University of California San Diego, San Diego, California, United States of America.
  • 14Department of Molecular Physiology and Biophysics and Center for Human Genetics Research, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
  • 15Department of Psychiatry, University of California San Diego, San Diego, California, United States of America.

Abstract

HIV sensory neuropathy and distal neuropathic pain (DNP) are common, disabling complications associated with combination antiretroviral therapy (cART). We previously associated iron-regulatory genetic polymorphisms with a reduced risk of HIV sensory neuropathy during more neurotoxic types of cART. We here evaluated the impact of polymorphisms in 19 iron-regulatory genes on DNP in 560 HIV-infected subjects from a prospective, observational study, who underwent neurological examinations to ascertain peripheral neuropathy and structured interviews to ascertain DNP. Genotype-DNP associations were explored by logistic regression and permutation-based analytical methods. Among 559 evaluable subjects, 331 (59%) developed HIV-SN, and 168 (30%) reported DNP. Fifteen polymorphisms in 8 genes (p<0.05) and 5 variants in 4 genes (p<0.01) were nominally associated with DNP: polymorphisms in TF, TFRC, BMP6, ACO1, SLC11A2, and FXN conferred reduced risk (adjusted odds ratios [ORs] ranging from 0.2 to 0.7, all p<0.05); other variants in TF, CP, ACO1, BMP6, and B2M conferred increased risk (ORs ranging from 1.3 to 3.1, all p<0.05). Risks associated with some variants were statistically significant either in black or white subgroups but were consistent in direction. ACO1 rs2026739 remained significantly associated with DNP in whites (permutation p<0.0001) after correction for multiple tests. Several of the same iron-regulatory-gene polymorphisms, including ACO1 rs2026739, were also associated with severity of DNP (all p<0.05). Common polymorphisms in iron-management genes are associated with DNP and with DNP severity in HIV-infected persons receiving cART. Consistent risk estimates across population subgroups and persistence of the ACO1 rs2026739 association after adjustment for multiple testing suggest that genetic variation in iron-regulation and transport modulates susceptibility to DNP.

PMID:
25144566
[PubMed - in process]
PMCID:
PMC4140681
Free PMC Article

Images from this publication.See all images (1)Free text

Figure 1
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Public Library of Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk