Hemochromatosis (HFE) Gene Variants Are Associated with Increased Mitochondrial DNA Levels During HIV-1 Infection and Antiretroviral Therapy

AIDS Res Hum Retroviruses. 2018 Nov;34(11):942-949. doi: 10.1089/AID.2018.0025. Epub 2018 Aug 22.

Abstract

Some HIV-associated complications involve mitochondrial dysfunction and may be less common in individuals with iron-loading HFE (hemochromatosis gene) variants. We evaluated HFE 845A and 187G alleles in relation to mitochondrial DNA (mtDNA) levels in peripheral blood mononuclear cells from 85 individuals with HIV infection on uninterrupted antiretroviral therapy (ART) for 15 or more consecutive weeks. Carriers of HFE gene variants (N = 24) had significantly higher mtDNA levels than noncarriers (N = 61), after adjusting for age, race, sex, and type of ART [adjusted β-coefficient 297, p-value < .001 for at least one HFE variant], but mtDNA declined among all individuals on study during 48 weeks on ART. Increased cellular mtDNA content may represent a compensatory response to mitochondrial stress that is influenced by iron-loading HFE variants.

Keywords: ART; HFE; allele; mtDNA.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Alleles
  • Anti-HIV Agents / adverse effects
  • Anti-HIV Agents / pharmacology*
  • Anti-HIV Agents / therapeutic use*
  • CD4 Lymphocyte Count
  • Case-Control Studies
  • DNA Copy Number Variations / drug effects
  • DNA, Mitochondrial / drug effects*
  • DNA, Mitochondrial / genetics
  • Female
  • Genotype
  • HIV Infections / drug therapy*
  • HIV Infections / genetics*
  • HIV-1
  • Hemochromatosis Protein / genetics*
  • Humans
  • Leukocytes, Mononuclear / drug effects
  • Male
  • Middle Aged
  • Mitochondria / drug effects
  • RNA, Viral / blood

Substances

  • Anti-HIV Agents
  • DNA, Mitochondrial
  • HFE protein, human
  • Hemochromatosis Protein
  • RNA, Viral