(SALT LAKE CITY)鈥揝cientists from the University of Utah School of Medicine are the first to show that a genetic variation in the IFITM3 gene is associated with a higher risk of developing coronary artery lesions in patients with Kawasaki disease鈥搑egarded as the leading cause of acquired heart disease among children in developed countries. This new finding, published in the May 13, 2014, issue of Molecular Genetics & Genomic Medicine, gives insight into potential mechanisms for Kawasaki disease and provides further evidence that viruses may play an important role in development of this inflammatory condition.
Kawasaki disease (KD) is a condition that causes inflammation in the walls of small- or medium-sized blood vessels throughout the body, including the coronary arteries that supply blood to the heart. Kawasaki disease typically affects children under 5 years old and researchers believe a viral infection triggers it, but so far, this theory has not been proved. KD occurs in the United States in 10 of every 100,000 children but is most prevalent in those of Asian ancestry, particularly Japanese and Korean.
"Previous research has shown that a gene called IFITM3 plays an important role in human resistance to viruses, such as influenza, and that people who have a particular variant of the IFITM3 gene are at increased risk of more severe flu infections," says John H. Weis, Ph.D., professor of pathology and George J. Weber Presidential Chair at the University of Utah (U of U) School of Medicine and senior author on the study. "One objective of our current study was to find out whether this genetic variation had a similar effect in Kawasaki disease."
The IFITM3 gene is one of approximately 300 genes that contribute to the body's defense against viral infections. Weis and a global team of collaborators analyzed the DNA of 140 patients with Kawasaki disease and found that those with this genetic variation in the IFITM3 gene were significantly more likely to develop coronary artery lesions or enlargement.
"Given our knowledge that this IFITM3 gene variant has been linked to a reduced ability to fight other viral infections, our data suggests that viruses may be an important causative agent for Kawasaki disease or the coronary artery lesions associated with it," says Weis.
Although KD is more common in children of Asian ethnicity, approximately 2,000 to 4,000 cases of Kawasaki disease are identified in the U.S. each year and the rate of diagnosis is increasing. As many as one in four children with untreated Kawasaki disease will develop coronary artery enlargement or aneurysms, which can be fatal.
"Even with appropriate treatment, 5 percent to 7 percent of children with KD develop coronary dilation," says Neil E. Bowles, Ph.D., research associate professor of pediatrics at the University of Utah School of Medicine and lead author on the study. "Until now, there has been no way to assess the risk of coronary artery lesions in Kawasaki disease."
In countries such as Japan, where Kawasaki disease is more common, screening for the IFITM3 gene variant potentially could help doctors identify patients at risk for serious coronary artery complications so they could monitor these patients more closely.
The IFITM3 gene variant evaluated in this study is present in approximately two-thirds of people of Pacific Rim Asian descent, but less than 5 percent of people of North American or Northern European descent. This may help to explain why Kawasaki disease occurs more often in Asian children, but larger studies are needed to establish a statistically significant link between this genetic variation and susceptibility to KD.
"We hope that the results of our study will spur new research into the key genes and proteins involved in Kawasaki disease and the development of coronary artery lesions," says Bowles.
In addition to continued investigation into the potential mechanisms involved in Kawasaki disease, future research will focus on the development of an animal model of KD for studying the immune response pathways involved in the disease.
"By applying discoveries made in mice to Kawasaki disease in humans, we've found a new link that could have significant implications on our understanding of the disease and our ability to treat it," says Weis. "This study really shows the importance and value of collaborations among scientists who are working on animal and human models of disease."