Deficiency of α-1-antitrypsin influences systemic iron homeostasis.

Published

Journal Article

There is evidence that proteases and antiproteases participate in the iron homeostasis of cells and living systems. We tested the postulate that α-1 antitrypsin (A1AT) polymorphism and the consequent deficiency of this antiprotease in humans are associated with a systemic disruption in iron homeostasis. Archived plasma samples from Alpha-1 Foundation (30 MM, 30 MZ, and 30 ZZ individuals) were analyzed for A1AT, ferritin, transferrin, and C-reactive protein (CRP). Plasma samples were also assayed for metals using inductively coupled plasma atomic emission spectroscopy (ICPAES). Plasma levels of A1AT in MZ and ZZ individuals were approximately 60% and 20% of those for MM individuals respectively. Plasma ferritin concentrations in those with the ZZ genotype were greater relative to those individuals with either MM or MZ genotype. Plasma transferrin for MM, MZ, and ZZ genotypes showed no significant differences. Linear regression analysis revealed a significant (negative) relationship between plasma concentrations of A1AT and ferritin while that between A1AT and transferrin levels was not significant. Plasma CRP concentrations were not significantly different between MM, MZ, and ZZ individuals. ICPAES measurement of metals confirmed elevated plasma concentrations of nonheme iron among ZZ individuals. Nonheme iron concentrations correlated (negatively) with levels of A1AT. A1AT deficiency is associated with evidence of a disruption in iron homeostasis with plasma ferritin and nonheme iron concentrations being elevated among those with the ZZ genotype.

Full Text

Duke Authors

Cited Authors

  • Ghio, AJ; Soukup, JM; Richards, JH; Fischer, BM; Voynow, JA; Schmechel, DE

Published Date

  • 2013

Published In

Volume / Issue

  • 8 /

Start / End Page

  • 45 - 51

PubMed ID

  • 23378755

Pubmed Central ID

  • 23378755

Electronic International Standard Serial Number (EISSN)

  • 1178-2005

Digital Object Identifier (DOI)

  • 10.2147/COPD.S37897

Language

  • eng

Conference Location

  • New Zealand