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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
NFKBIZ polymorphisms and susceptibility to pneumococcal disease in european and african populations
Genes and Immunity, Volume 11, No. 4, Year 2010
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Description
The proinflammatory transcription factor nuclear factor-B (NF-κB) has a central role in host defence against pneumococcal disease. Both rare mutations and common polymorphisms in the NFKBIA gene encoding the NF-κB inhibitor, IB-α, associate with susceptibility to bacterial disease, but the possible role of polymorphisms within the related IB-gene NFKBIZ in the development of invasive pneumococcal disease (IPD) has not been reported previously. To investigate this further, we examined the frequencies of 22 single-nucleotide polymorphisms spanning NFKBIZ in two case-control studies, comprising UK Caucasian (n1008) and Kenyan (n=723) individuals. Nine polymorphisms within a single UK linkage disequilibrium (LD) block and all four polymorphisms within the equivalent, shorter Kenyan LD block displayed either a significant association with IPD or a trend towards association. For each polymorphism, heterozygosity was associated with protection from IPD when compared with the combined homozygous states (for example, for rs600718, Mantel-Haenszel 2× 2 2 7.576, P0.006, odds ratio (OR)0.67, 95% confidence interval (95% CI) for OR: 0.51-0.88; for rs616597, Mantel-Haenszel 2 × 2 2 8.715, P0.003, OR0.65, 95% CI: 0.49-0.86). We conclude that multiple NFKBIZ polymorphisms associate with susceptibility to IPD in humans. The study of multiple populations may aid in fine mapping of associations within extensive regions of strong LD (transethnic mapping). © 2010 Macmillan Publishers Limited All rights reserved.
Authors & Co-Authors
Chapman, Stephen James
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
United Kingdom, Oxford
Churchill Hospital
Khor, Chiea Chuen
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
Singapore, Singapore City
A-star, Singapore Institute for Clinical Sciences
Vannberg, Fredrik O.
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
Rautanen, Anna
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
Segal, Shelley
United Kingdom, Oxford
John Radcliffe Hospital
Moore, Catrin E.
Viet Nam, Ho Chi Minh City
Cho Quan Hospital
Davies, Robert J.O.
United Kingdom, Oxford
Nihr Oxford Biomedical Research Centre
Day, Nichloas P.J.
Viet Nam, Ho Chi Minh City
Cho Quan Hospital
Peshu, Norbert M.
Kenya, Kilifi
Centre for Geographic Medicine Research
Crook, Derrick W.
United Kingdom, Oxford
John Radcliffe Hospital
Berkley, James A.
Kenya, Kilifi
Centre for Geographic Medicine Research
Williams, Thomas Neil
United Kingdom, Oxford
John Radcliffe Hospital
Kenya, Kilifi
Centre for Geographic Medicine Research
Ghana, Accra
Indepth Network
Scott, John Anthony Gerard
Kenya, Kilifi
Centre for Geographic Medicine Research
Hill, Adrian V. S.
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
Statistics
Citations: 36
Authors: 14
Affiliations: 8
Identifiers
Doi:
10.1038/gene.2009.76
ISSN:
14664879
Research Areas
Cancer
Genetics And Genomics
Study Design
Case-Control Study