Genetic variant decreases risk of severe malaria

By analyzing genomes of people in regions where malaria frequently occurs, an international team has identified a genetic variant that decreases the risk of severe malaria, according to a study appearing in Science.

Malaria is a life-threatening parasitic disease. It is caused by the Plasmodium parasites, which are often transmitted to people through the bites of infected female Anopheles mosquitoes. According to the WHO, in 2015, nearly half of the world's population was at risk of malaria in 2015, and there were 214 million new cases of malaria resulting in 438,000 deaths. The disease occurs most frequently in sub-Saharan Africa, but it also occurs in South-East Asia, Latin America, and the Middle East. Although the widespread use of new, more effective treatments has dramatically decreased the number of malaria deaths, the disease is still a serious public health problem.

Since malaria has high mortality, it has been suggested to place a strong selective pressure on the human genome. Human genetic resistance to malaria is an inherited change in the genome that confers a selective survival advantage. It is well known that Plasmodium parasites invade mammals via multiple interactions between parasite ligands and their receptors on red blood cells. Some studies indicated that natural resistance to malaria involves a cluster of receptor genes. But the underlying mechanism remains unclear.

The new study, led by researchers at the University of Oxford, describes a genetic variant affecting red blood cell invasion receptors and shows that this genetic variant provides some protection against malaria. The team analyzed genome sequence data from human populations, including 1269 people from sub-Saharan Africa. Results showed that a genetic variant that affects the host invasion receptor genes GYPA and GYPB is associated with a 40% reduced risk of severe malaria. People with the genetic variant were less likely to have severe complications of malaria.

GYPA and GYPB genes are located on chromosome 4q31. GYPA encodes a protein called glycophorin A and GYPB encodes glycophorin B. The genetic variant identified in this study appears to responsible for the fusion of glycophorin A and glycophorin B on red blood cells, leading to the formation of a hybrid glycophorin. “These findings link structural variation of red blood cell invasion receptors with natural resistance to severe malaria,” the researchers concluded.

Malaria parasites infect humans via cell surface protein-protein interactions. A deeper understanding of these interactions will aid in the design and development of intervention strategies. This study, which is led by researchers from many countries including the UK, the USA, the Gambia, Burkina Faso, Italy, Cameroon, Kenya, Tanzania, and Malawi, provide new insights into the mechanism of human genetic resistance to malaria. (Cusabio aims to provides high quality proteins including Recombinant Aqp2, GYPA and GYPB.)