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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.

Original publication

DOI

10.1038/sj.gene.6363877

Type

Journal article

Journal

Genes and immunity

Publication Date

08/2002

Volume

3

Pages

286 - 291

Addresses

Wellcome Trust Centre for Human Genetics, Oxford, UK.

Keywords

Chromosomes, Human, X, Animals, Humans, Pan troglodytes, Malaria, Falciparum, CD40 Ligand, DNA, Case-Control Studies, Base Sequence, Gene Frequency, Haplotypes, Phenotype, Alleles, Molecular Sequence Data, Gambia, Female, Male, Promoter Regions, Genetic, Genetic Variation