Asthma patients with a specific genetic profile exhibit more intense asthma symptoms following exposure to traffic pollution, according to NIEHS researchers and their collaborators at Rice University. The study appeared online Aug. 23 in the journal Scientific Reports.
The research team also found that asthma patients who lack this genetic profile do not have the same sensitivity to traffic pollution and do not experience worse asthma symptoms. The work brings scientists closer to being able to use precision medicine, an emerging field that intends to prevent and treat disease based on factors specific to an individual.
Co-lead author Shepherd Schurman, M.D., associate medical director of the NIEHS Clinical Research Unit (CRU), said the results are based on genetic variations, which are the subtle differences in DNA that make each person unique. To understand the concept, he suggested one think of human genes, which are made up of DNA base pairs A, C, G, and T, as written instructions for making proteins.
"All humans have the same genes, in other words the same basic instructions, but in some people one DNA base pair has been changed," Schurman said. "This common type of genetic variation is called a single nucleotide polymorphism, or SNP, and it can alter the way proteins are made, so that an individual is more or less prone to illness."
Schurman is also head of the Environmental Polymorphisms Registry, which is a DNA bank in North Carolina that provided volunteers for the study. The registry studies how SNPs impact disease risk in combination with environmental exposures.
Schurman collaborated with NIEHS colleague and lung disease expert Stavros Garantziotis, M.D., who is the CRU medical director. They examined four SNPs that are involved in a biochemical pathway that leads to inflammatory responses in the body.
Although SNPs are usually studied one at a time, they wanted to see if different combinations of these SNPs, along with pollution exposure, could worsen symptoms in a person with an inflammatory disease like asthma.
Schurman and Garantziotis gathered information about the SNPs, severity of asthma symptoms, and residential addresses of 2,704 registry participants with asthma. Using the SNPs data, they divided the participants into three groups: hyper-responders, or those very sensitive to air pollution and likely to develop inflammation; hypo-responders, or those insensitive to air pollution and less likely to develop inflammation; and those who were in between.
With the help of scientists at Rice University, the team used the participants’ addresses to calculate their distance from a major road. Participants were categorized depending on whether they lived less than or more than 275 yards from a major roadway. Data suggest that air pollution levels are elevated closer to major roads.
Results showed that asthma sufferers who were hyper-responders and lived closer to heavily travelled roads had the worst asthma symptoms, such as difficulty breathing, chest pain, cough, and wheezing, compared to the other groups.
In contrast, asthma patients who were hypo-responders and lived further away from busy roads had milder symptoms. Garantziotis said the work could greatly enhance the quality of life for people with asthma.
"Based on this research, we could propose that hyper-responders, who are exposed to traffic pollution, receive air purification intervention, such as HEPA filters, for their home," Garantziotis said.
NIEHS Clinical Director Janet Hall, M.D., said the results emphasize the importance of gene-environment interactions in the progression of disease. "This research is a great example of how we can approach disease prevention on a personal level, and tailor our treatments to suit individual patients," she said.
Citation: Schurman SH, Bravo MA, Innes CL, Jackson WB 2nd, McGrath JA, Miranda ML, Garantziotis S. 2018. Toll-like receptor 4 pathway polymorphisms interact with pollution to influence asthma diagnosis and severity. Sci Rep 8(1):12713.