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

dc.contributor.author Fischer, Bernard Martin
dc.contributor.author Ghio, Andrew J
dc.contributor.author Richards, JH
dc.contributor.author Schmechel, DE
dc.contributor.author Soukup, JM
dc.contributor.author Voynow, JA
dc.coverage.spatial New Zealand
dc.date.accessioned 2017-03-01T19:57:22Z
dc.date.available 2017-03-01T19:57:22Z
dc.date.issued 2013
dc.identifier https://www.ncbi.nlm.nih.gov/pubmed/23378755
dc.identifier copd-8-045
dc.identifier.uri http://hdl.handle.net/10161/13744
dc.description.abstract 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.
dc.language eng
dc.relation.ispartof Int J Chron Obstruct Pulmon Dis
dc.relation.isversionof 10.2147/COPD.S37897
dc.subject ferritin
dc.subject proteinase inhibitor proteins
dc.subject serpins
dc.subject transferrin
dc.subject α-1-antitrypsin deficiency
dc.subject Aluminum
dc.subject C-Reactive Protein
dc.subject Copper
dc.subject Female
dc.subject Ferritins
dc.subject Genotype
dc.subject Homeostasis
dc.subject Humans
dc.subject Iron
dc.subject Linear Models
dc.subject Male
dc.subject Middle Aged
dc.subject Polymorphism, Genetic
dc.subject Spectrophotometry, Atomic
dc.subject Transferrin
dc.subject alpha 1-Antitrypsin
dc.subject alpha 1-Antitrypsin Deficiency
dc.title Deficiency of α-1-antitrypsin influences systemic iron homeostasis.
dc.type Journal article
pubs.author-url https://www.ncbi.nlm.nih.gov/pubmed/23378755
pubs.begin-page 45
pubs.end-page 51
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Duke
pubs.organisational-group Faculty
pubs.organisational-group Pediatrics
pubs.organisational-group Pediatrics, Allergy and Immunology
pubs.organisational-group School of Medicine
pubs.publication-status Published
pubs.volume 8
dc.identifier.eissn 1178-2005


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