Researchers in South East Asia have identified two genetic variants that offer clues as to why some people are more susceptible to severe dengue than others.
The study, funded by the Wellcome Trust and the Agency for Science, Technology, and Research, Singapore, offers clues to how the body responds to dengue infection.
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, 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 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.
“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,” said Professor Cameron Simmons, senior author of the study from the Oxford University Clinical Research Unit, Vietnam.
Dr Khor Chiea Chuen, first author of the study, added: “This study implicates genetic variation in a molecule that activates natural killer cells as a culprit for increased susceptibility to severe Dengue.
“This is surprising as prior to this it was thought that defects in other components of the immune response, such as. T-cells, B-cells or dendritic cells, were responsible.”
The study was recently published in the journal Nature Genetics.