October 14, 2011 -- Researchers in South East Asia have identified two genetic variants associated with increased susceptibility to severe dengue. The study, funded by the Wellcome Trust and the Agency for Science, Technology, and Research (A*STAR), Singapore, offers clues to how the body responds to dengue infection.
Dengue is globally the most common mosquito-borne infection after malaria, with an estimated 100 million infections occurring annually. Symptoms range from mild to incapacitating high fever, with potentially life-threatening complications. No clinically-approved vaccine or specific treatments exist for the disease.
In children, severe dengue is characterised by increased vascular permeability, a state in which blood plasma is able to ‘leak’ from blood vessels to surrounding tissues. This is a potentially deadly complication that can lead to dengue shock syndrome – a life-threatening form of hypovolemic shock caused by a decrease in the volume of blood plasma. Epidemiological studies have suggested that certain populations are more susceptible to severe dengue, implying that some people’s genetic make-up makes them more susceptible to the disease.
To test this hypothesis, researchers at the Wellcome Trust Vietnam Research Programme and Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam, together with researchers from the Genome Institute of Singapore (GIS), a research institute under A*STAR, conducted the first ever genome-wide association study to compare the genomes of children with severe dengue against population controls. Initially, they compared 2,008 patients against 2,018 controls. They then replicated their findings in an independent follow-up sample of 1,737 cases and 2,934 controls.
The findings are published today in the journal Nature Genetics. The researchers identified changes in the DNA code located within two genes – MICB on chromosome 6 and PLCE1 on chromosome 10 – that appeared to increase a child’s susceptibility to dengue shock syndrome.