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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
CISH and susceptibility to infectious diseases
New England Journal of Medicine, Volume 362, No. 22, Year 2010
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Description
Background: The interleukin-2-mediated immune response is critical for host defense against infectious pathogens. Cytokine-inducible SRC homology 2 (SH2) domain protein (CISH), a suppressor of cytokine signaling, controls interleukin-2 signaling. Methods: Using a case-control design, we tested for an association between CISH polymorphisms and susceptibility to major infectious diseases (bacteremia, tuberculosis, and severe malaria) in blood samples from 8402 persons in Gambia, Hong Kong, Kenya, Malawi, and Vietnam. We had previously tested 20 other immune-related genes in one or more of these sample collections. Results: We observed associations between variant alleles of multiple CISH polymorphisms and increased susceptibility to each infectious disease in each of the study populations. When all five single-nucleotide polymorphisms (SNPs) (at positions -639, -292, -163, +1320, and +3415 [all relative to CISH]) within the CISH-associated locus were considered together in a multiple-SNP score, we found an association between CISH genetic variants and susceptibility to bacteremia, malaria, and tuberculosis (P = 3.8x10 -11 for all comparisons), with -292 accounting for most of the association signal (P = 4.58x10-7). Peripheral-blood mononuclear cells obtained from adult subjects carrying the -292 variant, as compared with wild-type cells, showed a muted response to the stimulation of interleukin-2 production - that is, 25 to 40% less CISH expression. Conclusions: Variants of CISH are associated with susceptibility to diseases caused by diverse infectious pathogens, suggesting that negative regulators of cytokine signaling have a role in immunity against various infectious diseases. The overall risk of one of these infectious diseases was increased by at least 18% among persons carrying the variant CISH alleles. Copyright © 2010 Massachusetts Medical Society.
Authors & Co-Authors
Khor, Chiea Chuen
Unknown Affiliation
Vannberg, Fredrik O.
Unknown Affiliation
Chapman, Stephen James
Unknown Affiliation
Guo, Haiyan
Unknown Affiliation
Wong, Sunny H.
Unknown Affiliation
Walley, Andrew J.
Unknown Affiliation
Vukcevic, Damjan
Unknown Affiliation
Rautanen, Anna
Unknown Affiliation
Mills, Tara C.
Unknown Affiliation
Chang, Kwok Chiu
Unknown Affiliation
Kam, Kaiman
Unknown Affiliation
Crampin, Amelia Catharine
Unknown Affiliation
Ngwira, Bagrey M.M.
Unknown Affiliation
Leung, Chichiu
Unknown Affiliation
Tam, Cheuk Ming
Unknown Affiliation
Chan, Chiu Yeung
Unknown Affiliation
Sung, Joseph
Unknown Affiliation
Yew, Wing W.
Unknown Affiliation
Toh, Kai Yee
Unknown Affiliation
Tay, Stacey K.H.
Unknown Affiliation
Kwiatkowski, Dominic P.
Unknown Affiliation
Lienhardt, Christian
Unknown Affiliation
Hien, Tran Tinh
Unknown Affiliation
Day, Nichloas P.J.
Unknown Affiliation
Peshu, Norbert M.
Unknown Affiliation
Marsh, Kevin
Unknown Affiliation
Maitland, Kathryn M.
Unknown Affiliation
Scott, John Anthony Gerard
Unknown Affiliation
Williams, Thomas Neil
Unknown Affiliation
Berkley, James A.
Unknown Affiliation
Floyd, Sian
Unknown Affiliation
Tang, Nelson L.S.
Unknown Affiliation
Fine, Paul E.M.
Unknown Affiliation
Goh, Denise L.M.
Unknown Affiliation
Hill, Adrian V.S.
Unknown Affiliation
Statistics
Citations: 66
Authors: 35
Affiliations: 17
Identifiers
Doi:
10.1056/NEJMoa0905606
ISSN:
00284793
e-ISSN:
15334406
Research Areas
Genetics And Genomics
Infectious Diseases
Study Design
Case-Control Study
Study Locations
Gambia
Kenya
Malawi