First genome-wide association study for dengue identifies candidate susceptibility genes
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."
More information: Chiea Chuen Khor et al. Genome-wide association study identifies susceptibility loci for Dengue shock syndrome at MICB and PLCE1. Nature Genetics; e-pub Oct. 16, 2011.
Provided by Wellcome Trust
- China alerts about dengue fever Oct 11, 2006 | not rated yet | 0
- New understanding of dengue fever could help with vaccine May 06, 2010 | not rated yet | 0
- Second dengue fever patient dies in Taiwan Nov 01, 2006 | not rated yet | 0
- Rural areas at higher risk of dengue fever than cities Aug 30, 2011 | not rated yet | 0
- Scientists prove hypothesis on the mystery of dengue virus infection Feb 11, 2010 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Classical and Quantum Mechanics via Lie algebras
Apr 15, 2011 I'd like to open a discussion thread for version 2 of the draft of my book ''Classical and Quantum Mechanics via Lie algebras'', available online at http://lanl.arxiv.org/abs/0810.1019 , and for the...
- More from Physics Forums - Independent Research
More news stories
Northwestern University scientists have shown a gene involved in neurodegenerative disease also plays a critical role in the proper function of the circadian clock.
Genetics May 16, 2013 | not rated yet | 0 |
Informed consent is the backbone of patient care. Genetic testing has long required patient consent and patients have had a "right not to know" the results. However, as 21st century medicine now begins to use the tools of ...
Genetics May 16, 2013 | 5 / 5 (1) | 3 |
Ethicists provide framework supporting new recommendations on reporting incidental findings in gene sequencing
In a paper published in Science Express, a group of experts led by bioethicists in the Center for Medical Ethics and Health Policy at Baylor College of Medicine provide a framework for the new American College of Medical Geneti ...
Genetics May 16, 2013 | not rated yet | 0
The use of genome-wide analysis (GWA), where the entirety of an individual's DNA is examined to look for the genomic mutations or variants which can cause health problems is a massively useful technology for diagnosing disease. ...
Genetics May 16, 2013 | not rated yet | 0
DNA databases might help identify victims of crime and human trafficking, but how do we safeguard the personal privacy of innocent victims and family members? A new report online May 15 in the Cell Press journal Trends in ...
Genetics May 15, 2013 | not rated yet | 0
An increasing number of U.S. children are experiencing gastrointestinal issues that require interventions to resolve, according to research presented at Digestive Disease Week (DDW).
10 hours ago | not rated yet | 0 |
The latest makeover to a massive psychiatric tome honored by some, reviled by others and even called the "Bible" of mental disorders is being released Saturday with a host of new changes.
8 hours ago | not rated yet | 0
A new case of the deadly coronavirus has been detected in Saudi Arabia where 15 people have already died after contracting it, the health ministry announced on Saturday on its Internet website.
8 hours ago | not rated yet | 0
Big names in medicine are set to give an upbeat assessment of the war on AIDS on Tuesday, 30 years after French researchers identified the virus that causes the disease.
18 hours ago | 5 / 5 (1) | 0
For combat veterans suffering from post-traumatic stress disorder, 'fear circuitry' in the brain never rests
Chronic trauma can inflict lasting damage to brain regions associated with fear and anxiety. Previous imaging studies of people with post-traumatic stress disorder, or PTSD, have shown that these brain regions can over-or ...
19 hours ago | 5 / 5 (1) | 0 |
A ground-breaking advance in colonoscopy technology signals the future of colorectal care, according to research presented today at Digestive Disease Week(DDW). Additional research focuses on optimizing the minimal withdrawal ...
10 hours ago | 5 / 5 (2) | 0