Navigation Links
First genome-wide association study for dengue identifies candidate susceptibility genes
Date:10/16/2011

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, 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 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, 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.

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 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 the 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 researchers believe that PLCE1 may also contribute to the normal functioning of the vascular endothelium, the thin layer of cells that lines the 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.

Professor Cameron Simmons, senior author of the study 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. 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."

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. However, they did not show up in our large, well-powered genome scan."

Combating infectious diseases is one the strategic priorities of the Wellcome Trust. Much of this work is carried out at a local level in regions where disease is endemic. This includes several major overseas programmes, including the Wellcome Trust's Vietnam Research Programme.

Commenting on the research, Professor Danny Altmann, Head of Pathogens, Immunology and Population Health at the Wellcome Trust, said: "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."


'/>"/>
Contact: Craig Brierley
c.brierley@wellcome.ac.uk
44-207-611-7329
Wellcome Trust
Source:Eurekalert

Related biology news :

1. New way to make malaria medicine also first step in finding new antibiotics
2. Complete Genomics launches, becomes worlds first large-scale human genome sequencing company
3. Digital zebrafish embryo provides the first complete developmental blueprint of a vertebrate
4. Synaptics to Report First Quarter Results on October 23
5. Alzheimers disease research attracts first partner
6. Volcanoes may have provided sparks and chemistry for first life
7. Study of polar dinosaur migration questions whether dinosaurs were truly the first great migrators
8. Synaptics Reports Record Results for First Quarter of Fiscal 2009
9. First comprehensive genomic study of common cold reveals new treatment targets
10. Scientists achieve first tracking of salmon from headwaters in Rockies through Pacific to Alaska
11. First results from hospital trials testing
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:1/4/2017)... , Jan. 4, 2017  CES 2017 – ... sensor technology, today announced the launch of two ... systems, the highly-accurate biometric sensor modules that incorporate ... technology, experience and expertise. The two new designs ... specifically for hearables, and Benchmark BW2.0, a 2-LED ...
(Date:12/22/2016)... 2016 SuperCom (NASDAQ:   ... the e-Government, Public Safety, HealthCare, and Finance sectors announced today that ... selected to implement and deploy a community-based supportive services program to ... , further expanding its presence in the state. ... This new program, which is ...
(Date:12/19/2016)... TORONTO , 19 de diciembre de 2016  Mosaic Biomedicals ... el desarrollo acelerado de MSC-1, un anticuerpo humanizado que se espera ... en 2017, con múltiples sitios previstos a lo largo de Europa ... MSC-1 ... factor inhibidor de leucemia (LIF), una citoquina pleiotrópica que se sobreexpresa ...
Breaking Biology News(10 mins):
(Date:1/18/2017)... ... January 18, 2017 , ... Researchers from a new study are stating that if ... after prostate cancer treatment, this indicates there is still remaining prostate cancer cells that are ... The PSA test has always been an indicator of whether a man’s prostate cancer ...
(Date:1/18/2017)... ... January 18, 2017 , ... uBiome, the leading ... by its Science Editor, Dr. Elisabeth Bik, in the December 2016 issue of ... joined uBiome in October 2016 from her previous position at Stanford University School ...
(Date:1/18/2017)... 18, 2017  HUYA Bioscience International, (HUYA), the leader ... pharmaceutical innovations, announced today a strategic collaboration ... Investment Company (referred to as CAS Innovation). The collaboration ... by leading scientists at CAS to meet the medical ... is the first company to have recognized ...
(Date:1/18/2017)...  Market Research Future published a half-cooked research report on Global ... at a CAGR of 12% during the period 2016 to 2022. ... ... cell division without any control. These abnormal cells have the ability ... cells can spread to other parts of the body through the ...
Breaking Biology Technology: