January 10, 2018—Researchers from Harvard T.H. Chan School of Public Health have identified a gene associated with lower asthma risk and its role in the disease’s progression—findings that open a new potential pathway for treatment.
Senior author Quan Lu, associate professor of environmental genetics and pathophysiology, and colleagues found a link between the gene GSDMB (gasdermin B) and asthma when they discovered that it is highly expressed in airway epithelial cells, and, when activated, induces cell pyroptosis—a form of cell death that is linked to inflammation and may contribute to asthma progression. The researchers also demonstrated that a variant of the gene protects against this biochemical activity, reducing asthma susceptibility.
“Our findings represent important advances in the field of asthma,” Lu said. “Identifying asthma genes and elucidating the disease’s biology are essential steps toward developing new, more effective therapies.”
Asthma affects more than 300 million people worldwide, but its molecular basis has been poorly understood. About 8% of the U.S. population is affected by the disease, and treatment costs top $50 billion each year.
Previous studies have identified a genetic region that is significantly associated with asthma risk called the 17q21 locus, which contains at least six genes. Most researchers, including Lu and his colleagues, expected that a gene called ORMDL3 would be the one linked to asthma risk. Instead, their study implicated its neighbor in the region, GSDMB.
The researchers studied DNA samples from more than 50,000 adult asthma patients participating in the Genetic Epidemiology Research in Adult Health and Aging cohort. They focused on genetic variants in the 17q21 locus that could alter protein coding. By combining genetic association analyses and mechanistic studies, they were able to zero in on GSDMB.
Their findings have important implications for potential asthma therapies that target GSDMB. For individuals with the right genetic profile, GSDMB could be suppressed, preventing airway epithelial pyroptosis and, ultimately, lowering asthma risk.