London:  Scientists have identified two genes which they claim increase a person's risk of getting dengue -- the most common mosquito-borne infection after malaria, with nearly 100 million infections occurring annually worldwide.

An international team has found changes in the DNA code located in two genes -- MICB on chromosome 6 and PLCE1 on chromosome 10 -- which increases a person's susceptibility to dengue shock syndrome, a discovery that offers vital clues to how the body responds to the infection.

MICB is known to play a role in the body's immune system and the team believes that a variant of this gene may affect the activation of natural killer cells or CD8 T-cells, two types of 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. This hypothesis is consistent with evidence that increased viral loads occur in tissues of patients with severe dengue.

Mutations in PLCE1 have previously been linked to nephrotic syndrome, a childhood disease characterised by impairment of the normal barrier and blood filtering functions of cells in the kidney.

The scientists believe that PLCE1 may also contribute to the normal functioning of the vascular endothelium, the thin layer of cells that lines interior surface of blood vessels, with some variants of PLCE1 predisposing an individual to leakage from the blood vessels, the hallmark clinical feature of dengue shock syndrome.

Lead author Prof Cameron Simmons from the Oxford University Clinical Research Unit, Vietnam, said: "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."

For their research, the scientists conducted the first ever genome-wide association study to compare genomes of children with severe dengue against population controls.

Initially, they compared 2,008 patients against 2,018 controls. They then replicated the findings in an independent follow-up sample of 1,737 cases and 2,934 controls, the latest edition of the 'Nature Genetics' journal reported.

According to team member Dr Khor Chiea Chuen: "This study implicates genetic variation within our natural killer cells as a highly suspicious culprit for increased susceptibility to severe dengue.

"This is extremely surprising as it was thought that defects in other components of the immune response, such as T-cells, B-cells or dendritic cells, were responsible. However they did not show up in our large, well-powered genome scan."

Prof Danny Altmann of the Wellcome Trust, which funded the research, added: "The World Health Organisation 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.

"This study, the first of its kind for dengue, is a step along the road towards understanding and eventually combating this deadly disease."

(Agencies)