Asthma associated with both genetics and environmental exposures

While progress has been made in identifying genes associated with asthma, the disease is complex, and its development is likely dependent upon both genetics and environmental exposures, according to a leading expert presenting at the annual meeting of the American College of Allergy, Asthma and Immunology (ACAAI) in Miami Beach, Fla.

On one hand, 39 potential "asthma genes" have been identified. Yet, for nearly every gene found to be negatively associated with asthma in one study, other studies have failed to replicate the findings.

"This suggests that the effect of these genes on allergic diseases is not direct and simple," said Fernando D. Martinez, M.D., director of Arizona Respiratory Center, interim director of the BIO5 Institute and Swift-McNear Professor of Pediatrics at the University of Arizona in Tucson, Ariz. "Many genetic variants associated with asthma will not increase the risk of the disease in all persons. Most will modulate the effects of environmental exposures, making certain subjects more or less susceptible."

With respect to environmental exposures worsening asthma, Dr. Martinez highlights viral infections, passive smoking and air pollution.

But the impact of all environmental factors isn't necessarily obvious. Some exposures play a protective role. "For example, in farming communities where exposure to microbial products is high, children have significantly less asthma and allergies," said Dr. Martinez.

In some cases, an allele (part of a gene) found to be a higher risk factor for allergic asthma in some individuals may be associated with less risk of developing asthma in others. Dr. Martinez names the CD14 gene as one such example. When people with a variant of this gene are exposed to high levels of endotoxin (a product present in bacteria), it protects them from developing an allergic response. But people with this same gene variant who are exposed to low levels of endotoxin are at higher risk of an allergy.

Research to indentify and understand the genes related to asthma is ongoing.

"We have identified many genetic variants associated with asthma and allergies," said Dr. Marteniz. "However, only a fraction of the variants have been discovered. A lot of work still needs to be done to uncover how these diseases are inherited."

Dr. Martinez suggests that the expectation that doctors will someday be able to predict asthma at birth should be replaced with an expectation that experts will be able to identify which children should or should not be exposed to certain environmental factors to lessen their risk of developing asthma.

"The hope is that by combining information on genetic markers and exposures, we will be able to identify even more accurately children at high-risk for different forms of asthma in the future," he said.

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