Mutations linked to repair of chromosome ends may make emphysema more likely in smokers

Jan. 15, 2015

Mutations in a gene that helps repair damaged chromosome ends may make smokers—especially female smokers—more susceptible to emphysema, according to results of a new study led by Johns Hopkins Kimmel Cancer Center researchers. A report on the research was published recently in the Journal of Clinical Investigation.

The mutations are one of a few genetic factors that have been directly linked to chronic obstructive pulmonary disease (COPD), including emphysema, since the 1960s, says Mary Armanios, MD, associate professor of oncology at the Johns Hopkins University School of Medicine.

Specifically, the alteration occurs in the telomerase reverse transcriptase (TERT) gene, which helps produce an enzyme called telomerase. Telomerase maintains and repairs the “caps” that protect the ends of chromosomes from degradation during cell division. Telomeres gradually shorten with age and act as a sort of cellular clock in cells. Mutations in TERT lead to excessively shortened telomeres.

Using genetic data gathered in COPD studies funded by the National Institutes of Health, Armanios and colleagues found TERT mutations in three of 292 smokers with emphysema. The researchers then looked at a sample of 50 Johns Hopkins patients with syndromes linked to telomere shortening. Among 39 nonsmokers, there were no cases of emphysema. Among smokers, seven of 11 patients, including all six female smokers, had emphysema. Armanios says this suggests that female smokers with telomerase-related mutations may be more susceptible to emphysema.

The researchers looked only at mutations in two telomerase genes but will now search for mutations in other telomere-regulating genes that might also predispose people to lung disease. “There are many genes that regulate the telomere, so it's likely that more than one percent could be impacted by these predisposing factors,” says Armanios.

Read the article at the Journal of Clinical Investigation website