Genetic key to severe malaria resistance uncovered

By Helen Albert, Senior medwireNews reporter

Researchers have identified two genetic variants linked with human resistance to severe malaria.

The team believes that the single nucleotide polymorphisms (SNPs), located within the ATP2B4 gene on chromosome 1 (rs4951074) and near MARVELD3 on chromosome 16 (rs2334880), may confer resistance to the disease by influencing steps in malaria development.

"Malaria causes approximately one million fatalities per year, mostly among African children. Although highlighted by the strong protective effect of the sickle-cell trait, the full impact of human genetics on resistance to the disease remains largely unexplored," say Christian Timmann (Bernard Nocht Institute for Tropical Medicine, Hamburg, Germany) and colleagues.

The researchers carried out a genome-wide association study (GWAS) in 2645 malaria patients and 3050 unaffected controls from Ghana in West Africa.

As reported in Nature, they discovered two novel SNPs associated with malaria resistance on chromosomes 1 and 16 and replicated two previously discovered associations.

The team explains that the ATP2B4 gene on chromosome 1 encodes the protein responsible for forming the main calcium pump in red blood cells. The ATP2B4 SNP may help inhibit parasite entry or growth in erythrocytes.

The MARVELD3 protein, which the chromosome 16 variant may influence, is expressed on endothelial cells and is thought to be linked to the microvascular damage that endothelial adherence of parasitized erythrocytes can cause. The team believes the variant may affect the way infected blood cells cross the barrier.

The two additional variants associated with resistance to severe malaria were the sickle-cell allele hemoglobin S in the HBB gene and a SNP in the ABO gene associated with blood group O. These had already been isolated in previous studies, and the current study results confirm the earlier findings.

"Both new association signals reported here lend themselves to a straightforward elaboration by cellular biology and, possibly, to medical application," write Timmann and co-workers.

These results indicate the potential use of GWAS in providing "candidates for the development of control measures against infectious diseases in humans," they conclude.

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