According to a study, two genetic variants that are linked with an increased susceptibility to severe dengue have been identified by investigators in South East Asia. The investigation provides insights into how the body responds to dengue, and was funded by the Wellcome Trust and the Agency for Science, Technology, and Research (A*STAR). The findings are published in the journal Nature Genetics.
After malaria, dengue is the most common mosquito-borne infection in the world. It occurs in sub-tropical and tropical areas of the world, affecting an estimated 100 million individuals each year. Symptoms usually appear between 3-14 days after the infective bite and range from mild to incapacitating high fever, severe headache, rash, joint and muscle pain and pain behind the eyes and even death. No treatment or clinically-approved vaccine for the disease exists.
Severe dengue in children, called dengue hemorrhagic fever, results in bleeding, low levels of blood platelets and blood plasma leakage into surrounding tissues caused through increased vascular permeability. This complication can be fatal as it can lead to dengue shock syndrome – a life threatening form of hypovolemic shock in which severe blood and fluid loss makes the heart unable to pump sufficient blood to the body. According to some Epidemiological investigations, certain populations are more susceptible to the disease, suggesting that some individual’s genetic make-up makes them more exposed.
In order to test this theory, investigators at the Wellcome Trust Vietnam Research Program and Oxford University Clinical Research Unit, Ho Chi Minh City, Vietna, collaborated with investigators from the Genome Institute of Singapore (GIS), a research institute under A*STAR, carried out the first ever genome-wide association investigation to analyze the difference in the genomes of children with severe dengue against population controls. Primarily they compared 2,008 children with severe dengue against 2,018 controls. Following this they then replicated their discoveries in an independent follow-up sample that involved 2,934 controls and 1,737 cases.
They identified changes in the DNA code within two genes – MICB on chromosome 6 and PLCE1 on chromosome 10 – that seemed to increase how susceptible children were to dengue shock syndrome.
Written by Grace Rattue