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Deficiency of a alpha-1-antitrypsin influences systemic iron homeostasis
Ghio, Andy, J. Soukup, J. Richards, B. Fischer, J. Voynow, AND D. Schmechel. Deficiency of a alpha-1-antitrypsin influences systemic iron homeostasis. International Journal of Chronic Obstructive Pulmonary Disease. Dove Medical Press, AUCKLAND, New Zealand, 2013(8):45-51, (2013).
One of many populations at risk for particle matter (PM) related injury are those individuals who lack alpha-1-antitrypsin. This paper tests the hypothesis that iron homeostasis may be a contributing factor to this groups sensitivity to PM.
Abstract Background: There is evidence that proteases and anti-proteases participate in the iron homeostasis of cells and living systems. We tested the postulate that alpha-1 antitrypsin (A1AT) polymorphism and the consequent deficiency of this anti-protease in humans are associated with a systemic disruption in iron homeostasis. Methods: 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). Results: 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 non-heme iron among ZZ individuals. Non-heme iron concentrations correlated (negatively) with levels of A1AT. Conclusions: A1AT deficiency is associated with evidence of a disruption in iron homeostasis with plasma ferritin and non-heme iron concentrations being elevated among those with the ZZ genotype.
Record Details:Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY
ENVIRONMENTAL PUBLIC HEALTH DIVISION