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Lack of association of interferon regulatory factor 1 with severe malaria in affected child-parental trio studies across three african populations

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Mangano, V. D., Clark, T. G., Auburn, S., Campino, S., Diakite, M., Fry, A. E., Green, A., Richardson, A., Jallow, M., Sisay-Joof, F., Pinder, M., Griffiths, M. J., Newton, C., Peshu, N., Williams, T. N., Marsh, Kevin, Molyneux, Malcolm E, Taylor, T. E., Modiano, D., Kwiatkowski, D. P. and Rockett, K. A. (2009) 'Lack of association of interferon regulatory factor 1 with severe malaria in affected child-parental trio studies across three african populations'. PLoS ONE, Vol 4, Issue 1, e4206.

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Abstract

Interferon Regulatory Factor 1 (IRF-1) is a member of the IRF family of transcription factors, which have key and diverse roles in the gene-regulatory networks of the immune system. IRF-1 has been described as a critical mediator of IFN-gamma signalling and as the major player in driving TH1 type responses. It is therefore likely to be crucial in both innate and adaptive responses against intracellular pathogens such as Plasmodium falciparum. Polymorphisms at the human IRF1 locus have been previously found to be associated with the ability to control P. falciparum infection in populations naturally exposed to malaria. In order to test whether genetic variation at the IRF1 locus also affects the risk of developing severe malaria, we performed a family-based test of association for 18 Single Nucleotide Polymorphisms (SNPs) across the gene in three African populations, using genotype data from 961 trios consisting of one affected child and his/her two parents (555 from The Gambia, 204 from Kenya and 202 from Malawi). No significant association with severe malaria or severe malaria subphenotypes (cerebral malaria and severe malaria anaemia) was observed for any of the SNPs/haplotypes tested in any of the study populations. Our results offer no evidence that the molecular pathways regulated by the transcription factor IRF-1 are involved in the immune-based pathogenesis of severe malaria.

Item Type: Article
Subjects: QW Microbiology and Immunology > Immunity by Type > QW 552 Active immunity
QW Microbiology and Immunology > Immunity by Type > QW 553 Maternally acquired immunity
QW Microbiology and Immunology > Immunity by Type > QW 551 Acquired immunity. Artificial immunity
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 680 Tropical diseases (General)
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 755 Epidemiology
WA Public Health > Health Problems of Special Population Groups > WA 395 Health in developing countries
QU Biochemistry > Genetics > QU 450 General Works
WB Practice of Medicine > Medical Climatology > WB 710 Diseases of geographic areas
WA Public Health > Preventive Medicine > WA 110 Prevention and control of communicable diseases. Transmission of infectious diseases
QW Microbiology and Immunology > Immunity by Type > QW 563 Local immunity
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 765 Prevention and control
QX Parasitology > Protozoa > QX 135 Plasmodia
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 695 Parasitic diseases (General)
WA Public Health > Preventive Medicine > WA 115 Immunization
QW Microbiology and Immunology > Immunity by Type > QW 541 Natural immunity. Immunogenetics
Faculty: Department: Groups (2002 - 2012) > Clinical Group
Digital Object Identifer (DOI): https://doi.org/10.1371/journal.pone.0004206
Depositing User: Users 43 not found.
Date Deposited: 01 Jun 2010 16:24
Last Modified: 06 Feb 2018 12:59
URI: http://archive.lstmed.ac.uk/id/eprint/322

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