Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Genetic Variant Protects People Against Malaria

08.11.2002


An international team of scientists has discovered a novel genetic trait that protects its carriers against the deadliest forms of malaria, while people without the trait are more likely to succumb to its fatal consequences.



This trait -- a mutation or “polymorphism” in the NOS2 gene -- controls the production of nitric oxide, a small chemical that can kill parasites and prevent malaria disease. Results of their study are published in the Nov. 9, 2002, issue of The Lancet.

The genetic variant explains why some people with malaria have only mild symptoms and recover fully, while others develop severe disease that may progress to death, said researchers from the University of Utah, the Durham Veterans Affairs (VA) Medical Center, Duke University Medical Center, the U.S. Centers for Disease Control and Prevention, Tanzania and Kenya.


“Malaria is a worldwide epidemic, affecting twice the population of the United States every year,” said Brice Weinberg, M.D., professor of medicine at the Durham VA and Duke University Medical Centers and principal investigator on the study. “Drug resistance to malaria is rampant, so our ability to artificially duplicate the benefits of this genetic trait would be enormous.”

People with the NOS2 gene variant make higher levels of nitric oxide, and the nitric oxide protects them from the extensive tissue and brain damage normally caused by the malaria parasite, said Dr. Maurine Hobbs, lead author and research assistant professor of internal medicine and human genetics at the University of Utah.

The team’s ultimate goal is to develop a simple treatment that boosts levels of nitric oxide to treat and prevent malaria, a prospect that the researchers say is well within their grasp.

Nitric oxide works by reducing the malaria parasites’ ability to multiply in liver and blood cells, preventing infected red blood cells from adhering to the lining of blood vessels, and decreasing the production of inflammatory chemicals (cytokines) that exacerbate the disease. Thus, it reduces the most deadly effects of malaria, which target the blood and vital organs such as the brain, said Dr. Nick Anstey, associate professor of medicine at the Menzies School for Health Research in Darwin, Australia.

While excessive nitric oxide can be harmful and causes inflammation in diseases such as arthritis, Anstey said that nitric oxide can also be beneficial by protecting against infections and preventing damage to cells and organs.

“Nitric oxide can be extremely useful when it is produced by the right cells, at the right levels, and at the right time,” said Anstey. Interestingly, he noted, the NOS2 gene variant does not prevent malarial infection; it simply renders the malaria parasite less harmful to bodily systems.

In fact, the NOS2 gene variant confers such overwhelming protection that Tanzanian carriers have an 88 percent lower risk of becoming ill with malaria than those without the trait, the study showed. In Kenya, its carriers have a 75 percent lower rate of developing severe malarial anemia. The two groups of patients consisted of 1,291 children who lived in highly mosquito- and malaria-infested areas of the two countries. The researchers analyzed blood and urine samples to demonstrate that people with the NOS2 polymorphism had higher levels of nitric oxide.

Weinberg said they believe that evolution has favored this protective mechanism for individuals who are most often exposed to malaria. Not surprisingly, then, Caucasians do not possess this genetic mutation, so they are at much higher risk for severe malaria. While malaria is seemingly a remote possibility in the heartland of America, the disease was once prevalent in the parts of the U.S. It was virtually eliminated by the 1940s through better mosquito control and improved living conditions, yet the disease periodically emerges in the U.S., even today.

Only about 1,200 malaria cases are reported in the U.S. yearly, and it is unlikely to ever reach epidemic proportions here, but malaria is rampant in much of Africa and Asia, infecting about 500 million people each year. Despite some advances in treatment, malaria continues to be deadly -- a malaria death occurs every 30 seconds worldwide.

Many of those infected with the malaria parasite may have no symptoms or only mild flu-like symptoms. However, others progress to more severe disease with extreme fatigue, fever, and chills. A third of these victims with severe disease -- mostly children and pregnant women -- succumb to more deadly consequences, either cerebral malaria or severe anemia.

In cerebral malaria, red blood cells containing the malaria parasite stick to the lining of blood vessels, causing blockages and decreasing blood supply to parts of the brain. Up to one-third of children with cerebral malaria die despite treatment. In severe anemia, parasites gobble up hemoglobin, destroy red blood cells and block blood formation until the patient is beyond rescue. Even with the best of current treatments, more than 1 million people die each year of severe malaria. The newly identified NOS2 gene polymorphism -- called C-1173T NOS2 -- protects against both kinds of malaria.

In addition to investigators from Duke, Utah, Australia and the CDC, researchers from the Hubert Kairuki Memorial University in Tanzania, and the World Health Organization in Switzerland contributed to the work. The research was supported by the National Institutes of Health, the U.S. Veterans Affairs, the U.S. Agency for International Development and the U.S. Centers for Disease Control and Prevention.

Rebecca Levine | EurekAlert!
Further information:
http://dukemednews.org/news/article.php?id=6008
http://www.mc.duke.edu/

More articles from Health and Medicine:

nachricht Investigators may unlock mystery of how staph cells dodge the body's immune system
22.09.2017 | Cedars-Sinai Medical Center

nachricht Monitoring the heart's mitochondria to predict cardiac arrest?
21.09.2017 | Boston Children's Hospital

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Rainbow colors reveal cell history: Uncovering β-cell heterogeneity

22.09.2017 | Life Sciences

Penn first in world to treat patient with new radiation technology

22.09.2017 | Medical Engineering

Calculating quietness

22.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>