Gene mutation causes asthma


Gene mutation causes asthma

A team of researchers at Weill Cornell Medical College, Columbia University Medical Center and SUNY Downstate Medical Center have found the cause of a common type of childhood asthma, and it's not rooted in allergens.

The way in which asthma develops is a subject of much scientific interest, considering that the way it develops and affects people varies considerably.

The team identified that an over-active gene "ORMDL3" was linked to around 30 percent of childhood asthma cases. The gene is responsible for disrupting the synthesis of lipid molecules (known as sphingolipids). They aren't fully sure how a reduced production of sphingolipids can cause asthma, yet the results of their study clearly indicate there is a link.

The study, published in Science Translational Medicine, revealed a completely unique pathway for asthma which does not have anything to do with allergens or inflammation.

The senior author of the study, Dr. Stefan Worgall, said:

"Usually asthma is thought to be an inflammatory disease or a reaction to an allergen. Our model shows that asthma can result from having too little of a type of sphingolipids. This is a completely new pathway for asthma pathogenesis. Our findings are not only valuable in understanding the pathogenesis of this complex disease, but provide a basis to develop novel therapies, especially asthma agents based on a patient's genotype."

As the most common "serious" childhood respiratory disease, a total of 7 million children in the U.S. suffer from asthma - it is a serious public health problem. In fact, almost one tenth of American teens have been diagnosed with asthma.

Asthma is more common among children living in big cities, mainly because exposure to traffic pollution near busy roads can cause chronic childhood asthma. In 2009, asthma was responsible for a total of 640,000 emergency room visits, 157,000 hospitalizations and 10.5 million missed school days in the USA.

Dr. Worgall added: "Yet while it has become increasingly evident that asthma takes several forms, treatment of the disorder is uniform. Most therapies are designed to reduce inflammation, but they do not help all sufferers."

In 2007, scientists discovered that the ORMDL3 gene mutation could up the risk of developing asthma by as much as 80 percent in a study that included more than 2,000 children.

Following a series of different genome-wide association studies (GWAS), the idea that asthma has more than just one form was finally accepted by the scientific community. The GWAS found a variation in the gene "ORMDL3" among 30 percent of asthma cases. The gene has been the most consistent genetic factor linked to the condition so far.

The researchers used mouse models to determine wether sphingolipid production might be connected to asthma. They found that inhibition of an enzyme crucial to sphingolipid synthesis, called serine palmitoyl-CoA transferase (SPT), triggered asthma among the mice.

In addition, airway hyperactivity among the mice was not caused by inflammation - magnesium treatment was ineffective in relieving chest tightness.

The study's first author, Dr. Tilla S. Worgall, assistant professor in the Department of Pathology and Cell Biology and a member of the Institute of Human Nutrition at Columbia University Medical Center, concluded:

"In our mouse models, we found that magnesium was not effective at inducing airway relaxation, suggesting the same would be true for humans whose asthma is linked to ORMDL3.

The association of decreased de novo sphingolipid synthesis with alterations in cellular magnesium homeostasis provides a clue into the mechanism of asthma. Therefore, therapies that circumvent the effect of the ORMDL3 genotype may be effective treatments for asthma sufferers. We are now working towards developing these new therapies."

Another useful avenue for developing new treatments for asthma stems from a previous study that found that people with asthma have a different blend of fungi in their lungs compared to "healthy" individuals.

Asthma Gene Study (Video Medical And Professional 2020).

Section Issues On Medicine: Disease