Carrying a variant form of a gene might add to a person’s risk of developing a devastating lung disease called pulmonary fibrosis. The variant induces the body to overproduce mucus in the lungs, researchers report in the April 21 New England Journal of Medicine.
Pulmonary fibrosis, a scarring of the lungs, is a rare but lethal condition that currently affects about 100,000 people in the United States. Although the cause of pulmonary fibrosis is unclear, scientists suspect a combination of genetic factors and environmental irritants such as exposure to cigarette smoke, asbestos fibers or silica dust.
There is no cure, and survival after diagnosis is often only three to five years, says James Kiley, a pulmonary physiologist at the National Heart, Lung and Blood Institute in Bethesda, Md., who wasn’t part of the new study. The findings might point to one of the root causes of pulmonary fibrosis, he says, “and may lead to something to prevent or manage this disease a bit better.”
Mucus protects air passages from foreign pathogens and pollutants. But too much mucus in the lungs can become sticky and difficult to clear, increasing susceptibility to infection and chronic inflammation. The delicate balance between maintaining a protective mucus coating and mucus overproduction is upset in certain lung diseases.
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In the new study, David Schwartz, a physician and immunologist at the University of Colorado School of Medicine and National Jewish Health in Denver, and his colleagues tested the genes of hundreds of people with healthy lungs and with pulmonary fibrosis. The patients included some who had family members with the disease and others who didn’t, in what are known as sporadic cases. The scientists examined genes that encode mucin proteins, the chief components of mucus.
A variant form of the mucin-5B gene, called MUC5B, stood out, showing up in 59 percent of people with familial forms of pulmonary fibrosis and 67 percent of those with sporadic pulmonary fibrosis, but in only 19 percent of the healthy group.
Compared with individuals who didn’t harbor the variant, people carrying one copy of the variant gene were about seven times as likely to develop pulmonary fibrosis if they also had a family member with the disease. People with one copy of the variant were nine times as likely to have the disease if they had no known relative with the condition. Carrying two copies of the variant form of MUC5B suggested even greater risk. But since the disease is rare, the absolute risk remains low even among people with the variant.
Genes are the blueprints for proteins. Further analyses indicated that having the MUC5B variant — a slightly altered blueprint — kept the gene switched on in lung cells. That resulted in excess manufacture of mucus, Schwartz says, which may account for part of the damage in these conditions. He and his colleagues hypothesize that mucus overproduction impairs lung immune defense and results in more lung injury from inhaled substances.