Ferroportin (SLC40A1) Q248H mutation is associated with lower circulating serum hepcidin levels in Rwandese HIV-positive women

Ann Hematol. 2012 Jun;91(6):911-6. doi: 10.1007/s00277-011-1400-3. Epub 2012 Jan 17.


The Q248H mutation in the gene SLC40A1 which encodes for the cellular iron exporter ferroportin is relatively common in Africa. This mutation has been associated with resistance to hepcidin and therefore we hypothesized that iron-related parameters and the prevalence of opportunistic infections in HIV might be influenced by the Q248H mutation. We conducted a cross-sectional study among 200 HIV-positive women in the Butare University Teaching Hospital in Rwanda. Polymerase chain reaction (PCR) and restriction enzyme digestion were used to identify the Q248H mutation. Physical examination was carried out and WHO HIV disease stage classification, complete blood count, CD4 count, indirect measures of iron status, serum hepcidin, and C-reactive protein concentrations were determined. The prevalence of ferroportin Q248H mutation was 6%. Subjects with ferroportin Q248H mutation had significantly higher values for serum ferritin (P = 0.001) and significantly lower values for serum hepcidin (P = 0.001) and transferrin (P = 0.01). Among the 12 HIV + Q248H heterozygotes, 8 suffered from at least one opportunistic infection. There was significantly higher prevalence of pulmonary TB (P = 0.01) and Pneumocystis jiroveci pneumonia (P = 0.02) in subjects with ferroportin Q248H mutation. Low hepcidin levels were found in ferroportin Q248H heterozygotes with HIV infection, notwithstanding the absence of anemia and the higher prevalence of some opportunistic infections. Hepcidin seems to be regulated in a different way in Q248H heterozygotes than is known thus far.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Amino Acid Substitution / genetics
  • Amino Acid Substitution / physiology
  • Antimicrobial Cationic Peptides / analysis
  • Antimicrobial Cationic Peptides / blood*
  • Cation Transport Proteins / genetics*
  • Cross-Sectional Studies
  • Female
  • Gene Frequency
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Glutamine / genetics
  • HIV Infections / blood*
  • HIV Infections / epidemiology
  • HIV Infections / ethnology
  • HIV Infections / genetics*
  • HIV Seropositivity / blood
  • HIV Seropositivity / epidemiology
  • HIV Seropositivity / ethnology
  • HIV Seropositivity / genetics
  • HIV-1 / physiology
  • Hepcidins
  • Histidine / genetics
  • Humans
  • Middle Aged
  • Mutation, Missense / physiology*
  • Osmolar Concentration
  • Rwanda / epidemiology
  • Young Adult


  • Antimicrobial Cationic Peptides
  • Cation Transport Proteins
  • HAMP protein, human
  • Hepcidins
  • metal transporting protein 1
  • Glutamine
  • Histidine