A specific gene variation associated with chronic obstructive pulmonary disease (COPD) is also linked with autoimmune disorders, according to a large genetic study, suggesting a role for autoimmune responses in the development of COPD.
The study, “A Phenome-Wide Association Study Uncovers a Role for Autoimmunity in the Development of Chronic Obstructive Pulmonary Disease,” was published in the American Journal of Respiratory Cell and Molecular Biology.
Although genome-wide association studies — which scan markers across the DNA of many people to find genetic variations associated with a particular disease — have identified diverse genes involved in the development of COPD, scientists still don’t fully understand the mechanisms of the disease.
A team led by Georgia State University and Vanderbilt University Medical Center researchers have now assessed the association between genetic variants in COPD and clinical characteristics, such as disease history, to obtain a more complete picture of the biological mechanisms behind COPD.
“Because there’s no treatment right now for COPD, we’re trying to figure out whether we can diagnose or prognose this disease earlier to prevent it,” Xiangming Ji, PhD, the study’s lead author and an assistant professor in the Byrdine F. Lewis College of Nursing and Health Professions at Georgia State, said in a press release.
The team analyzed genetic data from individuals participating in BioVU, Vanderbilt’s DNA biobank. They performed a so-called phenome-wide association study of 16 previously reported COPD-associated single nucleotide polymorphisms (SNPs) — the most common type of genetic variation, referring to differences in a single DNA building block, called a nucleotide.
Data were available from 18,335 adults of European descent, and the team used unique codes for different symptoms of disease. They identified 1,805 COPD cases with two or more phenotype codes. The patients were a median age of 64, comprised of 54% women and 67% who had ever smoked.
The findings replicated the link between six of the 16 SNPs and COPD. Importantly, one specific SNP — rs2074488 — was associated with COPD and bronchiectasis, as well as with autoimmune diseases like Type 1 diabetes and rheumatoid arthritis.
“The association between rs2074488 and several autoimmune disorders and bronchiectasis suggests a genetic link between autoimmune disease and COPD,” the researchers wrote in the study.
Prior studies had shown that rs2074488 correlates with Type 1 diabetes, rheumatoid arthritis, and a biomarker of COPD called serum surfactant protein D, but each disease was addressed separately.
“This SNP is also associated with several autoimmune diseases, like type 1 diabetes and rheumatoid arthritis, which suggests a genetic link between autoimmune disease and COPD. Many years ago, people believed that one of the causes of COPD is because the autoimmune system attacks its own lungs. We kind of confirmed that by our big data,” Ji said.
These findings are in line with increasing evidence that autoimmunity — or an immune attack against body’s own tissues — is involved in the development of COPD. Patients with this condition have increased levels of immune cells called T- and B-cells in the lungs, as well as autoantibodies targeting the pulmonary epithelium, which lines most of the respiratory tract.
“Our findings suggest that future research should target the role of the immune system in the pathogenesis of COPD,” the investigators wrote. Studies of how normal SNPs are related to COPD are also warranted, they also noted.
According to Ji, the results could ultimately open new avenues for using medications effective in autoimmune diseases for the treatment of COPD, since the disease also involves autoimmune responses.