Deficiency of α-1-antitrypsin influences systemic iron homeostasis.
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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.
proteinase inhibitor proteins
alpha 1-Antitrypsin Deficiency
Published Version (Please cite this version)10.2147/COPD.S37897
Publication InfoFischer, Bernard Martin; Ghio, Andrew J; Richards, JH; Schmechel, DE; Soukup, JM; & Voynow, JA (2013). Deficiency of α-1-antitrypsin influences systemic iron homeostasis. Int J Chron Obstruct Pulmon Dis, 8. pp. 45-51. 10.2147/COPD.S37897. Retrieved from https://hdl.handle.net/10161/13744.
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Associate Professor of Pediatrics
Comparative Pharmacology and Cell Biology Mechanisms of complementary-alternative medicines and products Signal Transduction and Cell Signaling Development of both animal and in vitro models of disease Implications of early life lung injury on long-term immune function and overall health Mechanisms of inflammation and disease Cytokine, Oxidant, and Inflammatory Mediator NetworkingIntegrative care/treatments for HIV patientsMechanisms of chronic inf
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