Skip to main content
Top
Published in: Malaria Journal 1/2008

Open Access 01-12-2008 | Research

NCF1 gene and pseudogene pattern: association with parasitic infection and autoimmunity

Authors: Bernhard Greve, Peter Hoffmann, Reinhard Vonthein, Jürgen Kun, Bertrand Lell, Marcin P Mycko, Krysztof W Selmaj, Klaus Berger, Robert Weissert, Peter G Kremsner

Published in: Malaria Journal | Issue 1/2008

Login to get access

Abstract

Background

Neutrophil cytosolic factor 1, p47phox (NCF1) is a component of the leukocyte NADPH oxidase complex mediating formation of reactive oxygen intermediates (ROI) which play an important role in host defense and autoimmunity. An individual genomic pattern of ncf1 and its two types of pseudogenes (reflected by the ΔGT/GTGT ratio) may influence the individual capacity to produce ROI.

Methods

NCF1ΔGT/GTGT ratios were correlated with clinical parameters and ROI production during Plasmodium falciparum malaria and with susceptibility to the autoimmune disease multiple sclerosis (MS).

Results

Among Gabonese children with severe malaria, ROI production from peripheral blood tended to be higher in individuals with a ΔGT/GTGT ratio ≤ 1:1. ΔGT/GTGT ratios were not associated with susceptibility to MS, but to age-of-onset among MS patients.

Conclusion

The genomic pattern of NCF1 and its pseudogenes might influence ROI production but only marginally influence susceptibility to and outcome of malaria and MS.
Appendix
Available only for authorised users
Literature
1.
go back to reference Rosen GM, Pou S, Ramos CL, Cohen MS, Britigan BE: Free radicals and phagocytic cells. FASEB J. 1995, 9: 200-209.PubMed Rosen GM, Pou S, Ramos CL, Cohen MS, Britigan BE: Free radicals and phagocytic cells. FASEB J. 1995, 9: 200-209.PubMed
2.
go back to reference Greve B, Kremsner PG, Lell B, Luckner D, Schmid D: Malarial anaemia in African children associated with high oxygen-radical production. Lancet. 2000, 355: 40-41. 10.1016/S0140-6736(99)04761-3.CrossRefPubMed Greve B, Kremsner PG, Lell B, Luckner D, Schmid D: Malarial anaemia in African children associated with high oxygen-radical production. Lancet. 2000, 355: 40-41. 10.1016/S0140-6736(99)04761-3.CrossRefPubMed
3.
go back to reference Greve B, Lehman LG, Lell B, Luckner D, Schmidt-Ott R, Kremsner PG: High oxygen radical production is associated with fast parasite clearance in children with Plasmodium falciparum malaria. J Infect Dis. 1999, 179: 1584-1586. 10.1086/314780.CrossRefPubMed Greve B, Lehman LG, Lell B, Luckner D, Schmidt-Ott R, Kremsner PG: High oxygen radical production is associated with fast parasite clearance in children with Plasmodium falciparum malaria. J Infect Dis. 1999, 179: 1584-1586. 10.1086/314780.CrossRefPubMed
4.
go back to reference Kamata H, Hirata H: Redox regulation of cellular signalling. Cell Signal. 1999, 11: 1-14. 10.1016/S0898-6568(98)00037-0.CrossRefPubMed Kamata H, Hirata H: Redox regulation of cellular signalling. Cell Signal. 1999, 11: 1-14. 10.1016/S0898-6568(98)00037-0.CrossRefPubMed
5.
go back to reference Gilgun-Sherki Y, Melamed E, Offen D: The role of oxidative stress in the pathogenesis of multiple sclerosis: the need for effective antioxidant therapy. J Neurol. 2004, 251: 261-268. 10.1007/s00415-004-0348-9.CrossRefPubMed Gilgun-Sherki Y, Melamed E, Offen D: The role of oxidative stress in the pathogenesis of multiple sclerosis: the need for effective antioxidant therapy. J Neurol. 2004, 251: 261-268. 10.1007/s00415-004-0348-9.CrossRefPubMed
6.
go back to reference Smith KJ, Kapoor R, Felts PA: Demyelination: the role of reactive oxygen and nitrogen species. Brain Pathol. 1999, 9: 69-92.CrossRefPubMed Smith KJ, Kapoor R, Felts PA: Demyelination: the role of reactive oxygen and nitrogen species. Brain Pathol. 1999, 9: 69-92.CrossRefPubMed
7.
go back to reference Ferretti G, Bacchetti T, DiLudovico F, Viti B, Angeleri VA, Danni M, Provinciali L: Intracellular oxidative activity and respiratory burst of leukocytes isolated from multiple sclerosis patients. Neurochem Int. 2006, 48: 87-92. 10.1016/j.neuint.2005.09.005.CrossRefPubMed Ferretti G, Bacchetti T, DiLudovico F, Viti B, Angeleri VA, Danni M, Provinciali L: Intracellular oxidative activity and respiratory burst of leukocytes isolated from multiple sclerosis patients. Neurochem Int. 2006, 48: 87-92. 10.1016/j.neuint.2005.09.005.CrossRefPubMed
8.
go back to reference Heyworth PG, Cross AR, Curnutte JT: Chronic granulomatous disease. Curr Opin Immunol. 2003, 15: 578-584. 10.1016/S0952-7915(03)00109-2.CrossRefPubMed Heyworth PG, Cross AR, Curnutte JT: Chronic granulomatous disease. Curr Opin Immunol. 2003, 15: 578-584. 10.1016/S0952-7915(03)00109-2.CrossRefPubMed
9.
go back to reference Uhlemann AC, Szlezak NA, Vonthein R, Tomiuk J, Emmer SA, Lell B, Kremsner PG, Kun JF: DNA phasing by TA dinucleotide microsatellite length determines in vitro and in vivo expression of the gp91phox subunit of NADPH oxidase and mediates protection against severe malaria. J Infect Dis. 2004, 189: 2227-2234. 10.1086/421242.CrossRefPubMed Uhlemann AC, Szlezak NA, Vonthein R, Tomiuk J, Emmer SA, Lell B, Kremsner PG, Kun JF: DNA phasing by TA dinucleotide microsatellite length determines in vitro and in vivo expression of the gp91phox subunit of NADPH oxidase and mediates protection against severe malaria. J Infect Dis. 2004, 189: 2227-2234. 10.1086/421242.CrossRefPubMed
10.
go back to reference Olsson LM, Lindqvist AK, Kallberg H, Padyukov L, Burkhardt H, Alfredsson L, Klareskog L, Holmdahl R: A case-control study of rheumatoid arthritis identifies an associated single nucleotide polymorphism in the NCF4 gene, supporting a role for the NADPH-oxidase complex in autoimmunity. Arthritis Res Ther. 2007, 9: R98-10.1186/ar2299.PubMedCentralCrossRefPubMed Olsson LM, Lindqvist AK, Kallberg H, Padyukov L, Burkhardt H, Alfredsson L, Klareskog L, Holmdahl R: A case-control study of rheumatoid arthritis identifies an associated single nucleotide polymorphism in the NCF4 gene, supporting a role for the NADPH-oxidase complex in autoimmunity. Arthritis Res Ther. 2007, 9: R98-10.1186/ar2299.PubMedCentralCrossRefPubMed
11.
go back to reference Hultqvist M, Holmdahl R: Ncf1 (p47phox) polymorphism determines oxidative burst and the severity of arthritis in rats and mice. Cell Immunol. 2005, 233: 97-101. 10.1016/j.cellimm.2005.04.008.CrossRefPubMed Hultqvist M, Holmdahl R: Ncf1 (p47phox) polymorphism determines oxidative burst and the severity of arthritis in rats and mice. Cell Immunol. 2005, 233: 97-101. 10.1016/j.cellimm.2005.04.008.CrossRefPubMed
12.
go back to reference Hultqvist M, Olofsson P, Holmberg J, Backstrom BT, Tordsson J, Holmdahl R: Enhanced autoimmunity, arthritis, and encephalomyelitis in mice with a reduced oxidative burst due to a mutation in the Ncf1 gene. Proc Natl Acad Sci USA. 2004, 101: 12646-12651. 10.1073/pnas.0403831101.PubMedCentralCrossRefPubMed Hultqvist M, Olofsson P, Holmberg J, Backstrom BT, Tordsson J, Holmdahl R: Enhanced autoimmunity, arthritis, and encephalomyelitis in mice with a reduced oxidative burst due to a mutation in the Ncf1 gene. Proc Natl Acad Sci USA. 2004, 101: 12646-12651. 10.1073/pnas.0403831101.PubMedCentralCrossRefPubMed
13.
go back to reference Olofsson P, Holmberg J, Tordsson J, Lu S, Akerstrom B, Holmdahl R: Positional identification of Ncf1 as a gene that regulates arthritis severity in rats. Nat Genet. 2003, 33: 25-32. 10.1038/ng1058.CrossRefPubMed Olofsson P, Holmberg J, Tordsson J, Lu S, Akerstrom B, Holmdahl R: Positional identification of Ncf1 as a gene that regulates arthritis severity in rats. Nat Genet. 2003, 33: 25-32. 10.1038/ng1058.CrossRefPubMed
14.
go back to reference Gelderman KA, Hultqvist M, Pizzolla A, Zhao M, Nandakumar KS, Mattsson R, Holmdahl R: Macrophages suppress T cell responses and arthritis development in mice by producing reactive oxygen species. J Clin Invest. 2007, 117: 3020-3028. 10.1172/JCI31935.PubMedCentralCrossRefPubMed Gelderman KA, Hultqvist M, Pizzolla A, Zhao M, Nandakumar KS, Mattsson R, Holmdahl R: Macrophages suppress T cell responses and arthritis development in mice by producing reactive oxygen species. J Clin Invest. 2007, 117: 3020-3028. 10.1172/JCI31935.PubMedCentralCrossRefPubMed
15.
go back to reference Heyworth PG, Noack D, Cross AR: Identification of a novel NCF-1 (p47-phox) pseudogene not containing the signature GT deletion: significance for A47 degrees chronic granulomatous disease carrier detection. Blood. 2002, 100: 1845-1851. 10.1182/blood-2002-03-0861.CrossRefPubMed Heyworth PG, Noack D, Cross AR: Identification of a novel NCF-1 (p47-phox) pseudogene not containing the signature GT deletion: significance for A47 degrees chronic granulomatous disease carrier detection. Blood. 2002, 100: 1845-1851. 10.1182/blood-2002-03-0861.CrossRefPubMed
16.
go back to reference Poser CM, Paty DW, Scheinberg L, McDonald WI, Davis FA, Ebers GC, Johnson KP, Sibley WA, Silberberg DH, Tourtellotte WW: New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol. 1983, 13: 227-231. 10.1002/ana.410130302.CrossRefPubMed Poser CM, Paty DW, Scheinberg L, McDonald WI, Davis FA, Ebers GC, Johnson KP, Sibley WA, Silberberg DH, Tourtellotte WW: New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol. 1983, 13: 227-231. 10.1002/ana.410130302.CrossRefPubMed
17.
go back to reference McDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, Lublin FD, McFarland HF, Paty DW, Polman CH, Reingold SC, Sandberg-Wollheim M, Sibley W, Thompson A, Noort van den S, Weinshenker BY, Wolinsky JS: Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol. 2001, 50: 121-127. 10.1002/ana.1032.CrossRefPubMed McDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, Lublin FD, McFarland HF, Paty DW, Polman CH, Reingold SC, Sandberg-Wollheim M, Sibley W, Thompson A, Noort van den S, Weinshenker BY, Wolinsky JS: Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol. 2001, 50: 121-127. 10.1002/ana.1032.CrossRefPubMed
18.
go back to reference Kun JF, Schmidt-Ott RJ, Lehman LG, Lell B, Luckner D, Greve B, Matousek P, Kremsner PG: Merozoite surface antigen 1 and 2 genotypes and rosetting of Plasmodium falciparum in severe and mild malaria in Lambarene, Gabon. Trans R Soc Trop Med Hyg. 1998, 92: 110-114. 10.1016/S0035-9203(98)90979-8.CrossRefPubMed Kun JF, Schmidt-Ott RJ, Lehman LG, Lell B, Luckner D, Greve B, Matousek P, Kremsner PG: Merozoite surface antigen 1 and 2 genotypes and rosetting of Plasmodium falciparum in severe and mild malaria in Lambarene, Gabon. Trans R Soc Trop Med Hyg. 1998, 92: 110-114. 10.1016/S0035-9203(98)90979-8.CrossRefPubMed
19.
go back to reference Kun JF, Mordmuller B, Lell B, Lehman LG, Luckner D, Kremsner PG: Polymorphism in promoter region of inducible nitric oxide synthase gene and protection against malaria. Lancet. 1998, 351: 265-266. 10.1016/S0140-6736(05)78273-8.CrossRefPubMed Kun JF, Mordmuller B, Lell B, Lehman LG, Luckner D, Kremsner PG: Polymorphism in promoter region of inducible nitric oxide synthase gene and protection against malaria. Lancet. 1998, 351: 265-266. 10.1016/S0140-6736(05)78273-8.CrossRefPubMed
20.
go back to reference Dekker J, de Boer M, Roos D: Gene-scan method for the recognition of carriers and patients with p47(phox)-deficient autosomal recessive chronic granulomatous disease. Exp Hematol. 2001, 29: 1319-1325. 10.1016/S0301-472X(01)00731-7.CrossRefPubMed Dekker J, de Boer M, Roos D: Gene-scan method for the recognition of carriers and patients with p47(phox)-deficient autosomal recessive chronic granulomatous disease. Exp Hematol. 2001, 29: 1319-1325. 10.1016/S0301-472X(01)00731-7.CrossRefPubMed
21.
go back to reference Suraweera N, Zampeli E, Rogers P, Atkin W, Forbes A, Harbord M, Silver A: NCF1 (p47phox) and ncf1 pseudogenes are not associated with inflammatory bowel disease. Inflamm Bowel Dis. 2004, 10: 758-762. 10.1097/00054725-200411000-00010.CrossRefPubMed Suraweera N, Zampeli E, Rogers P, Atkin W, Forbes A, Harbord M, Silver A: NCF1 (p47phox) and ncf1 pseudogenes are not associated with inflammatory bowel disease. Inflamm Bowel Dis. 2004, 10: 758-762. 10.1097/00054725-200411000-00010.CrossRefPubMed
22.
go back to reference Del Campo M, Antonell A, Magano LF, Munoz FJ, Flores R, Bayes M, Perez Jurado LA: Hemizygosity at the NCF1 gene in patients with Williams-Beuren syndrome decreases their risk of hypertension. Am J Hum Genet. 2006, 78: 533-542. 10.1086/501073.PubMedCentralCrossRefPubMed Del Campo M, Antonell A, Magano LF, Munoz FJ, Flores R, Bayes M, Perez Jurado LA: Hemizygosity at the NCF1 gene in patients with Williams-Beuren syndrome decreases their risk of hypertension. Am J Hum Genet. 2006, 78: 533-542. 10.1086/501073.PubMedCentralCrossRefPubMed
23.
go back to reference Harbord M, Hankin A, Bloom S, Mitchison H: Association between p47phox pseudogenes and inflammatory bowel disease. Blood. 2003, 101: 3337-10.1182/blood-2002-10-3060.CrossRefPubMed Harbord M, Hankin A, Bloom S, Mitchison H: Association between p47phox pseudogenes and inflammatory bowel disease. Blood. 2003, 101: 3337-10.1182/blood-2002-10-3060.CrossRefPubMed
Metadata
Title
NCF1 gene and pseudogene pattern: association with parasitic infection and autoimmunity
Authors
Bernhard Greve
Peter Hoffmann
Reinhard Vonthein
Jürgen Kun
Bertrand Lell
Marcin P Mycko
Krysztof W Selmaj
Klaus Berger
Robert Weissert
Peter G Kremsner
Publication date
01-12-2008
Publisher
BioMed Central
Published in
Malaria Journal / Issue 1/2008
Electronic ISSN: 1475-2875
DOI
https://doi.org/10.1186/1475-2875-7-251

Other articles of this Issue 1/2008

Malaria Journal 1/2008 Go to the issue