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Malaria Risk Muted in African Individuals Carrying Expression-Related SNPs

Editor's Note: The article described below is not yet available at the PNAS site but is scheduled to be posted this week.

For a paper set to appear in PNAS this week, a National Institutes of Health-led team looks at ties between malaria vulnerability and human leukocyte antigen (HLA) class I allotype-related expression of TAPBP, a gene coding for a peptide-loading complex component called tapasin that contributes to cell surface peptide presentation. After identifying SNPs linked to TAPBP expression in transcription factor and microRNA binding sites in individuals of African ancestry, the researchers attempted to untangle the impacts of these variants on malaria parasite Plasmodium falciparum susceptibility and malaria risk. The two TAPBP expression-related SNPs "associated with lower Plasmodium falciparum parasite prevalence and lower incidence of clinical malaria, specifically among individuals carrying tapasin-dependent HLA-I allotypes, presumably by augmenting peptide loading," the authors report, "whereas tapasin-independent allotypes associated with relative protection, regardless of imputed TAPBP [messenger RNA] expression levels."