HFE gene mutations and oxidative stress influence serum ferritin, associated with vascular damage, in hemodialysis patients

Am J Nephrol. 2007;27(1):101-7. doi: 10.1159/000099635. Epub 2007 Feb 13.

Abstract

Background/aims: Hyperferritinemia has been associated with cardiovascular mortality in hemodialysis patients. The aim of this study was to evaluate whether serum ferritin was affected by iron and oxidative status and by genetic factors (HFE mutations and the Ala9Val MnSOD polymorphism), and to assess the association between ferritin and cardiovascular damage evaluated by ecocolor-Doppler.

Methods: 63 hemodialysis patients were tested for HFE and MnSOD genotype by restriction analysis and oxidative status; vascular damage was assessed by measuring intima-media thickness, and by detecting plaques at carotid and femoral arteries.

Results: Ferritin was correlated with transferrin saturation (p = 0.003), decreased iron-specific serum antioxidant activity (p = 0.01), age (p = 0.03), and C282Y and H63D HFE mutations (p = 0.05), but not with the MnSOD polymorphism. Ferritin was associated with advanced vascular damage, as evaluated by the presence of plaques, both at carotid (p = 0.03) and femoral arteries (p = 0.001), the other risk factors being age and low albumin. Low iron-specific antioxidant activity was associated with carotid plaques (p = 0.03).

Conclusion: In hemodialysis patients, hyperferritinemia reflects a relative increase in iron availability and a decrease in iron-specific antioxidant activity, is favored by HFE mutations, and represents a risk factor for advanced cardiovascular damage.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Atherosclerosis / blood
  • Atherosclerosis / etiology
  • Atherosclerosis / genetics*
  • Blood Flow Velocity / physiology
  • Carotid Arteries / diagnostic imaging
  • Carotid Arteries / physiopathology
  • DNA / genetics*
  • Disease Progression
  • Female
  • Femoral Artery / diagnostic imaging
  • Femoral Artery / physiopathology
  • Ferritins / blood*
  • Genotype
  • Hemochromatosis Protein
  • Histocompatibility Antigens Class I / genetics*
  • Humans
  • Kidney Failure, Chronic / blood
  • Kidney Failure, Chronic / therapy
  • Male
  • Membrane Proteins / genetics*
  • Middle Aged
  • Mutation*
  • Oxidative Stress / physiology*
  • Polymorphism, Genetic
  • Prognosis
  • Renal Dialysis / adverse effects*
  • Retrospective Studies
  • Severity of Illness Index
  • Ultrasonography

Substances

  • HFE protein, human
  • Hemochromatosis Protein
  • Histocompatibility Antigens Class I
  • Membrane Proteins
  • DNA
  • Ferritins