Malaria risk reduced by genetic predisposition for cell suicide

Severe malaria is a major public health burden in Sub-Saharan Africa, where approximately one million individuals die each year as a result of infection with Plasmodium falciparum. Whereas adults in endemic areas develop some resistance to malaria, preventing severe complications, children under the age of five years can develop life-threatening forms of the disease. To date, the molecular mechanisms causing these manifestations are poorly understood.

FAS encodes for CD95, a molecule critically involved in the programmed death of some white blood cells. This candidate gene study, including more than 6,000 child subjects, details how a single nucleotide variant of FAS predisposes its carriers to a higher number of immune cells prone to suicide. These findings indicate that a genetic predisposition to an increased expression of CD95 may help to protect from severe malaria, possibly by rendering a type of white blood cell more susceptible to programmed cell death.

Kathrin Schuldt, co-author, said, "We believe that our study will help to unravel the mechanisms causing the fatal forms of malaria."

More information: Schuldt K, Kretz CC, Timmann C, Sievertsen J, Ehmen C, et al. (2011) A 2436C.A Polymorphism in the Human FAS Gene Promoter Associated with Severe Childhood Malaria. PLoS Genet 7(5): e1002066. doi:10.1371/journal.pgen.1002066

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