ArticlePLoS genetics2011
A -436C>A polymorphism in the human FAS gene promoter associated with severe childhood malaria.
Article in PLoS genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 20 citations in OpenAlex.
- A fused deep learning approach to transform drug repositioning.Communications chemistry · 2025Article
- Association of apoptosis-related variants to malaria infection and parasite density in individuals from the Brazilian Amazon.Malaria journal · 2023Article
- Lack of Association of CD55 Receptor Genetic Variants and Severe Malaria in Ghanaian Children.G3 (Bethesda, Md.) · 2017Article
- Differential positive selection of malaria resistance genes in three indigenous populations of Peninsular Malaysia.Human genetics · 2015Article
- Impairment of T cell function in parasitic infections.PLoS neglected tropical diseases · 2014Review
- Endothelial protein C receptor gene variants not associated with severe malaria in ghanaian children.PloS one · 2014Article
- MBL2 variations and malaria susceptibility in Indian populations.Infection and immunity · 2014Article
- Fc γ receptor IIIB (FcγRIIIB) polymorphisms are associated with clinical malaria in Ghanaian children.PloS one · 2012Article
- Sickle cell protection from malaria.Hematology reports · 2011Article
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Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human genetics and immune responses are considered to critically influence the outcome of malaria infections including life-threatening syndromes caused by Plasmodium falciparum. An important role in immune regulation is assigned to the apoptosis-signaling cell surface receptor CD95 (Fas, APO-1), encoded by the gene FAS. Here, a candidate-gene association study including variant discovery at the FAS gene locus was carried out in a case-control group comprising 1,195 pediatric cases of severe falciparum malaria and 769 unaffected controls from a region highly endemic for malaria in Ghana, West Africa. We found the A allele of c.-436C>A (rs9658676) located in the promoter region of FAS to be significantly associated with protection from severe childhood malaria (odds ratio 0.71, 95% confidence interval 0.58-0.88, p(empirical) = 0.02) and confirmed this finding in a replication group of 1,412 additional severe malaria cases and 2,659 community controls from the same geographic area. The combined analysis resulted in an odds ratio of 0.71 (95% confidence interval 0.62-0.80, p = 1.8×10⁻⁷, n = 6035). The association applied to c.-436AA homozygotes (odds ratio 0.47, 95% confidence interval 0.36-0.60) and to a lesser extent to c.-436AC heterozygotes (odds ratio 0.73, 95% confidence interval 0.63-0.84), and also to all phenotypic subgroups studied, including severe malaria anemia, cerebral malaria, and other malaria complications. Quantitative FACS analyses assessing CD95 surface expression of peripheral blood mononuclear cells of naïve donors showed a significantly higher proportion of CD69+CD95+ cells among persons homozygous for the protective A allele compared to AC heterozygotes and CC homozygotes, indicating a functional role of the associated CD95 variant, possibly in supporting lymphocyte apoptosis.
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