Imperial College London
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Professor Thomas N Williams

Faculty of Medicine, Department of Surgery & Cancer

Chair in Haemoglobinopathy Research
 
 
 
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Contact

 

tom.williams Website

 
 
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Location

 

Norfolk PlaceSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Khor:2007:10.1038/sj.gene.6364417,
author = {Khor, CC and Vannberg, FO and Chapman, SJ and Walley, A and Aucan, C and Loke, H and White, NJ and Peto, T and Khor, LK and Kwiatkowski, D and Day, N and Scott, A and Berkley, JA and Marsh, K and Peshu, N and Maitland, K and Williams, TN and Hill, AVS},
doi = {10.1038/sj.gene.6364417},
journal = {Genes and Immunity},
pages = {570--576},
title = {Positive replication and linkage disequilibrium mapping of the chromosome 21q22.1 malaria susceptibility locus},
url = {http://dx.doi.org/10.1038/sj.gene.6364417},
volume = {8},
year = {2007}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Four cytokine receptor genes are located on Chr21q22.11, encoding the α and β subunits of the interferon-α receptor (IFNAR1 and IFNAR2), the β subunit of the interleukin 10 receptor (IL10RB) and the second subunit of the interferon-γ receptor (IFNGR2). We previously reported that two variants in IFNAR1 were associated with susceptibility to malaria in Gambians. We now present an extensive fine-scale mapping of the associated region utilizing 45 additional genetic markers obtained from public databases and by sequencing a 44 kb region in and around the IFNAR1 gene in 24 Gambian children (12 cases/12 controls). Within the IFNAR1 gene, a newly studied C → G single-nucleotide polymorphism (IFNAR1 272354c-g) at position −576 relative to the transcription start was found to be more strongly associated with susceptibility to severe malaria. Association was observed in three populations: in Gambian (P=0.002), Kenyan (P=0.022) and Vietnamese (P=0.005) case–control studies. When all three studies were combined, using the Mantel–Haenszel test, the presence of IFNAR1 −576G was associated with a substantially elevated risk of severe malaria (N=2444, OR=1.38, 95% CI: 1.17–1.64; P=1.7 × 10−4). This study builds on previous work to further highlight the importance of the type-I interferon pathway in malaria susceptibility and illustrates the utility of typing SNPs within regions of high linkage disequilibrium in multiple populations to confirm initial positive associations.
AU  - Khor,CC
AU  - Vannberg,FO
AU  - Chapman,SJ
AU  - Walley,A
AU  - Aucan,C
AU  - Loke,H
AU  - White,NJ
AU  - Peto,T
AU  - Khor,LK
AU  - Kwiatkowski,D
AU  - Day,N
AU  - Scott,A
AU  - Berkley,JA
AU  - Marsh,K
AU  - Peshu,N
AU  - Maitland,K
AU  - Williams,TN
AU  - Hill,AVS
DO  - 10.1038/sj.gene.6364417
EP  - 576
PY  - 2007///
SN  - 1466-4879
SP  - 570
TI  - Positive replication and linkage disequilibrium mapping of the chromosome 21q22.1 malaria susceptibility locus
T2  - Genes and Immunity
UR  - http://dx.doi.org/10.1038/sj.gene.6364417
UR  - https://www.nature.com/articles/6364417
UR  - http://hdl.handle.net/10044/1/111171
VL  - 8
ER  -
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