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Variation in the ICAM1 gene is not associated with severe malaria phenotypes

Fry, A. E., Auburn, S., Diakite, M., Green, A., Richardson, A., Wilson, J., Jallow, M., Sisay-Joof, F., Pinder, M., Griffiths, M. J., Peshu, N., Williams, T. N., Marsh, Kevin, Molyneux, Malcolm E, Taylor, T. E., Rockett, K. A. and Kwiatkowski, D. P. (2008) 'Variation in the ICAM1 gene is not associated with severe malaria phenotypes'. Genes and Immunity, Vol 9, Issue 5, pp. 462-469.

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Abstract

Evidence from autopsy and in vitro binding studies suggests that adhesion of erythrocytes infected with Plasmodium falciparum to the human host intercellular adhesion molecule (ICAM)-1 receptor is important in the pathogenesis of severe malaria. Previous association studies between polymorphisms in the ICAM1 gene and susceptibility to severe malarial phenotypes have been inconclusive and often contradictory. We performed genetic association studies with 15 single nucleotide polymorphisms (SNPs) around the ICAM1 locus. All SNPs were screened in a family study of 1071 trios from The Gambia, Malawi and Kenya. Two key non-synonymous SNPs with previously reported associations, rs5491 (K56M or 'ICAM-1(Kilifi)') and rs5498 (K469E), were tested in an additional 708 Gambian trios and a case-control study of 4058 individuals. None of the polymorphisms were associated with severe malaria phenotypes. Pooled results across our studies for ICAM-1(Kilifi) were, in severe malaria, odds ratio (OR) 1.02, 95% confidence interval (CI) 0.96-1.09, P = 0.54, and cerebral malaria OR 1.07, CI 0.97-1.17, P = 0.17. We assess the available epidemiological, population genetic and functional evidence that links ICAM-1(Kilifi) to severe malaria susceptibility.

Item Type: Article
Uncontrolled Keywords: icam-1 plasmodium falciparum genetic association study intercellular-adhesion molecule-1 plasmodium-falciparum malaria family-based tests n-terminal domain cerebral malaria infected erythrocytes natural-selection binding-sites children receptor
Subjects: WC Communicable Diseases > Tropical and Parasitic Diseases > WC 755.1 General coverage
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 755 Epidemiology
QU Biochemistry > Cells and Genetics > QU 300 General works
QU Biochemistry > Genetics > QU 475 Genetic processes
QU Biochemistry > Genetics > QU 450 General Works
QY Clinical Pathology > Blood. Blood Chemistry > QY 400 General works
WB Practice of Medicine > Medical Climatology > WB 710 Diseases of geographic areas
QZ Pathology > Manifestations of Disease > QZ 140 General manifestations of disease > QZ 150 Local reactions to injury and disease
QX Parasitology > Protozoa > QX 135 Plasmodia
QX Parasitology > QX 45 Host-parasite relations
WH Hemic and Lymphatic Systems > WH 100 General works
QY Clinical Pathology > Diagnostic Tests > QY 250 Immunodiagnostic tests
Faculty: Department: Groups (2002 - 2012) > Clinical Group
Digital Object Identifer (DOI): https://doi.org/10.1038/gene.2008.38
Depositing User: Users 43 not found.
Date Deposited: 25 Jun 2010 10:55
Last Modified: 06 Feb 2018 13:00
URI: http://archive.lstmed.ac.uk/id/eprint/781

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