Gene Mutations Affect Inhalant Response.

• Position: Human response to inhaled endotoxin - Brief Article

Researchers at the University of Iowa, Iowa City, have found the first genetic evidence that mutations to a certain gene are associated with differences in the human response to inhaled endotoxin, a contaminant commonly found in agricultural dust, air pollution, and household dust. They determined that mutations in the toll-like receptor-4 (TLR4) gene can cause some people to be less responsive to inhaled endotoxin and less prone to develop an asthma-like reaction when exposed to this common environmental contaminant.

"In a fairly large study population of healthy individuals, we found that commonly occurring changes in the genetic sequence of TLR4 can make an individual more likely to be resistant to inhaled endotoxin than those who do not have the mutations," David A. Schwartz, professor of internal medicine, explains. "However, related studies with mice suggest that people with these mutations of TLR4 who are less responsive to inhaled endotoxin may prove to be more susceptible to systemic effects of endotoxin when they develop a blood-borne infection."

The team studied the response of 83 healthy individuals to increasing doses of endotoxin that equaled the amount a grain handler or farmer would be exposed to over the course of a normal eight-hour work shift. The participants had no heart or lung disease, history of cigarette smoking, or indication of even a tendency toward asthma. Thirty-one of the participants were hyporesponsive, or less responsive, to the bronchoconstrictive effects of endotoxin, while 52 had normal responses, meaning that they experienced chest tightness and other asthma-like symptoms. Seven of the 31 hyporesponsive participants had TLR4 mutations. In contrast, three...