CD40L association with protection from severe malaria.

CD40 ligand (CD40L), a glycoprotein involved in B cell proliferation, antigen presenting cell activation, and Ig class switching, is important in the immune response to infection. Rare coding mutations in CD40L can lead to life-threatening immunodeficiency but the potential for common variants to al...

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Auteurs principaux: Sabeti, P, Usen, S, Farhadian, S, Jallow, M, Doherty, T, Newport, M, Pinder, M, Ward, R, Kwiatkowski, D
Format: Journal article
Langue:English
Publié: 2002
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author Sabeti, P
Usen, S
Farhadian, S
Jallow, M
Doherty, T
Newport, M
Pinder, M
Ward, R
Kwiatkowski, D
author_facet Sabeti, P
Usen, S
Farhadian, S
Jallow, M
Doherty, T
Newport, M
Pinder, M
Ward, R
Kwiatkowski, D
author_sort Sabeti, P
collection OXFORD
description CD40 ligand (CD40L), a glycoprotein involved in B cell proliferation, antigen presenting cell activation, and Ig class switching, is important in the immune response to infection. Rare coding mutations in CD40L can lead to life-threatening immunodeficiency but the potential for common variants to alter disease susceptibility remains to be explored. To identify polymorphisms in CD40L, we sequenced 2.3 kb of the 5' flanking region and the first exon of the gene in DNA samples from 36 Gambian females and one chimpanzee. Diversity was lower than the average reported for other areas of the X chromosome, and only two polymorphisms were identified. The polymorphisms were genotyped in DNA samples from 957 Gambian individuals, cases and controls from a study of severe malaria. A significant reduction in risk for severe malaria (OR = 0.52, P = 0.002) was associated with males hemizygous for the CD40L-726C. Analysis by transmission disequilibrium test of 371 cases, for whom DNA from both parents was also available, confirmed the result was not due to stratification (P = 0.04). A similar but non-significant trend was found in females. This preliminary association of a common variant in CD40L with a malaria resistance phenotype encourages further genetic characterization of the role of CD40L in infectious disease.
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spelling oxford-uuid:3b15e1e4-22f3-448c-b55b-eec84c4d11512022-03-26T14:05:30ZCD40L association with protection from severe malaria.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:3b15e1e4-22f3-448c-b55b-eec84c4d1151EnglishSymplectic Elements at Oxford2002Sabeti, PUsen, SFarhadian, SJallow, MDoherty, TNewport, MPinder, MWard, RKwiatkowski, DCD40 ligand (CD40L), a glycoprotein involved in B cell proliferation, antigen presenting cell activation, and Ig class switching, is important in the immune response to infection. Rare coding mutations in CD40L can lead to life-threatening immunodeficiency but the potential for common variants to alter disease susceptibility remains to be explored. To identify polymorphisms in CD40L, we sequenced 2.3 kb of the 5' flanking region and the first exon of the gene in DNA samples from 36 Gambian females and one chimpanzee. Diversity was lower than the average reported for other areas of the X chromosome, and only two polymorphisms were identified. The polymorphisms were genotyped in DNA samples from 957 Gambian individuals, cases and controls from a study of severe malaria. A significant reduction in risk for severe malaria (OR = 0.52, P = 0.002) was associated with males hemizygous for the CD40L-726C. Analysis by transmission disequilibrium test of 371 cases, for whom DNA from both parents was also available, confirmed the result was not due to stratification (P = 0.04). A similar but non-significant trend was found in females. This preliminary association of a common variant in CD40L with a malaria resistance phenotype encourages further genetic characterization of the role of CD40L in infectious disease.
spellingShingle Sabeti, P
Usen, S
Farhadian, S
Jallow, M
Doherty, T
Newport, M
Pinder, M
Ward, R
Kwiatkowski, D
CD40L association with protection from severe malaria.
title CD40L association with protection from severe malaria.
title_full CD40L association with protection from severe malaria.
title_fullStr CD40L association with protection from severe malaria.
title_full_unstemmed CD40L association with protection from severe malaria.
title_short CD40L association with protection from severe malaria.
title_sort cd40l association with protection from severe malaria
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