title: Deficiency of α-1-antitrypsin influences systemic iron homeostasis.
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.
authors: Human Studies Facility, US Environmental Protection Agency, 104 Mason Farm Rd., Chapel Hill, NC 27599, USA. ghio.andy@epa.gov
authors: Andrew J
authors: AJ
authors: Ghio
authors: Joleen M
authors: JM
authors: Soukup
authors: Judy H
authors: JH
authors: Richards
authors: Bernard M
authors: BM
authors: Fischer
authors: Judith A
authors: JA
authors: Voynow
authors: Donald E
authors: DE
authors: Schmechel
mesh_terms: D000535:Aluminum / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D003300:Copper / Q000097:blood; D005260:Female; D005293:Ferritins / Q000097:blood*; D005838:Genotype; D006706:Homeostasis; D006801:Humans; D007501:Iron / Q000097:blood; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D013054:Spectrophotometry, Atomic; D014168:Transferrin / Q000032:analysis*; D000515:alpha 1-Antitrypsin / Q000097:blood*; D019896:alpha 1-Antitrypsin Deficiency / Q000235:genetics*
chemical_list: D014168:Transferrin; D000515:alpha 1-Antitrypsin; D003300:Copper; D002097:C-Reactive Protein; D005293:Ferritins; D000535:Aluminum; D007501:Iron
keywords: ferritin; proteinase inhibitor proteins; serpins; transferrin; α-1-antitrypsin deficiency
references: Mol Microbiol. 1992 Feb;6(3):337-44
references: 1552848
references: Exp Lung Res. 1988;14(5):671-86
references: 3224598
references: Biochim Biophys Acta. 2009 Jul;1790(7):731-9
references: 19100311
references: Infect Immun. 1996 Jan;64(1):182-8
references: 8557338
references: J Hepatol. 1997 Oct;27(4):716-25
references: 9365048
references: Lancet. 2005 Jun 25-Jul 1;365(9478):2225-36
references: 15978931
references: Am J Respir Crit Care Med. 2006 May 15;173(10):1072-7
references: 16439713
references: Infect Immun. 1993 Dec;61(12):5049-55
references: 8225581
references: Biochem J. 1993 Feb 15;290 ( Pt 1):109-13
references: 7679893
references: J Clin Invest. 1995 Jun;95(6):2491-500
references: 7769095
references: Infect Immun. 1994 Sep;62(9):4021-7
references: 8063422
references: Biochem Pharmacol. 2002 Oct 1;64(7):1139-45
references: 12234617
references: Best Pract Res Clin Haematol. 2002 Jun;15(2):411-26
references: 12401315
references: Proc Am Thorac Soc. 2010 Nov;7(6):381-6
references: 21030517
references: Semin Liver Dis. 1996 Feb;16(1):97-101
references: 8723327
references: Microbiol Immunol. 2001;45(8):579-90
references: 11592632
references: Chest. 2010 Nov;138(5):1116-24
references: 20634282
references: Biochem J. 1996 Nov 1;319 ( Pt 3):897-902
references: 8920996
references: Eur Respir J. 2009 Aug;34(2):346-53
references: 19324958
references: Thorax. 2004 Feb;59(2):164-9
references: 14760160
references: Oral Microbiol Immunol. 2001 Apr;16(2):79-87
references: 11240860
references: Hepatology. 1992 Jul;16(1):145-8
references: 1618466
references: J Hepatol. 2009 Jan;50(1):174-83
references: 19008010
references: Gut. 1978 Jun;19(6):538-42
references: 680587
references: J Food Prot. 1999 Dec;62(12):1475-7
references: 10606155
references: J Lab Clin Med. 1981 Mar;97(3):396-402
references: 6257809
references: Clin Transl Sci. 2009 Oct;2(5):333-9
references: 20411049
references: Orphanet J Rare Dis. 2011 Apr 12;6:14
references: 21486454
references: Exp Hematol. 1998 Oct;26(11):1053-60
references: 9766445
references: J Biol Chem. 2002 Jan 25;277(4):2385-95
references: 11694506
references: Am J Respir Crit Care Med. 2000 Aug;162(2 Pt 1):553-8
references: 10934086
references: Am J Respir Crit Care Med. 1999 Sep;160(3):796-801
references: 10471599
references: Hepatology. 1993 Sep;18(3):707-8
references: 8359811
references: Eur Respir J. 2004 Aug;24(2):286-91
references: 15332399
references: Clin Infect Dis. 2001 Aug 1;33(3):413-4
references: 11438916
references: J Bacteriol. 1982 Aug;151(2):783-7
references: 6807961
references: Bull World Health Organ. 1997;75(5):397-415
references: 9447774
references: Biochim Biophys Acta. 1998 Feb 4;1401(2):170-6
references: 9531972
references: Biochim Biophys Acta. 1983 Sep 13;759(3):229-35
references: 6349699
references: Stem Cells. 1997;15(4):291-6
references: 9253113