Dengue is globally the most common mosquito-borne infection after malaria. 100 million infections are estimated to occur annually.
Symptoms range from mild to incapacitating high fever, with potentially life-threatening complications. No vaccine or specific treatments exist for the disease. In children, severe dengue can lead to dengue shock syndrome, which is potentially life-threatening.
Previous studies have suggested that certain populations are more susceptible to severe dengue, implying that some people’s genetic make-up can lead them to be more susceptible.
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, set out to test this hypothesis.
They 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 study, funded by the Wellcome Trust and the Singapore Agency for Science, Technology, and Research, is published in the journal Nature Genetics.
Professor Cameron Simmons, senior author of the study from the Oxford University Clinical Research Unit in Vietnam, says: ‘Dengue is a potentially life-threatening disease. Our study confirms epidemiological evidence that some people are naturally more susceptible to severe forms of the disease than others. Our findings offer tantalising clues as to why this should be the case and open up new avenues for us to explore to help us understand the disease.’
The researchers identified changes in the DNA code located within two genes that appeared to increase a child’s susceptibility to dengue shock syndrome. The genes were MICB on chromosome 6 and PLCE1 on chromosome 10.
MICB is known to play a role the body’s immune system and the researchers believe that a variant of this gene may affect the activation of specific types of immune cells that play a key role in combating viral infection. If these cells are not properly functioning, their ability to rid the body of the dengue virus becomes impaired.
The researchers believe that some variants of PLCE1 may predispose an individual to leakage from the blood vessels, the hallmark clinical feature of dengue shock syndrome.
Professor Danny Altmann, Head of Pathogens, Immunology and Population Health at the Wellcome Trust, says: ‘The World Health Organization estimates that two-fifths of the world’s population – 2.5 billion people – are at risk from dengue infection, yet we still do not have any specific treatments or licensed vaccines. This study, the first of its kind for dengue, is a step along the road towards understanding and eventually combating this deadly disease.’