Could a genetic variation help identify high-risk flu patients?

Researchers have uncovered a genetic variation in the gene IFITM3 that may help identify patients at high risk for severe influenza. In addition, the team investigated the mechanism behind this association, uncovering the gene’s importance in cytotoxic T cells.

IFITM3 is a known antiviral protein and previous research has identified a link between an IFITM3 variant and flu severity in Chinese patients. However, this variant is rare in individuals of European ancestry, moreover, the underlying mechanism was unclear. Therefore this study, published recently in Nature Medicine, began by searching for other IFITM3 variants that might be associated with influenza risk.

The team, led by St. Jude Children’s Research Hospital (PI, USA), screened 393 influenza patients ranging from infants to 70+ years of age, discovering an IFITM3 variant termed rs34481144 that correlated to flu risk.

In three different groups of patients, all from the US, the researchers observed that individuals possessing one or more copies of high-risk rs34481144 were two-times more likely to develop severe flu symptoms than those with protective variants. For example, in a cohort of 86 patients from Memphis (PI, USA) almost two-thirds of flu patients with severe symptoms possessed the rs34481144 variant, compared with just 32% of individuals in the group with milder symptoms.

The team then investigated the mechanism behind IFITM3, discovering that those with the high-risk variant appeared to have reduced levels of IFITM3 in cytotoxic T cells, compared with those lacking this variant. In addition, the patients with the rs34481144 variation also were observed to possess lower numbers of cytotoxic T cells.

By exploring the variant further, the researchers discovered this variation was located in the region of IFITM3 involved in regulating gene expression, demonstrating there were significant differences in the binding of proteins that could suppress gene activity when comparing rs34481144 with the protective variant.

Author, Paul Thomas from St. Jude, commented:  “While this research focused on flu infections, the mechanism we identified has implications for regulating many genes involved in antiviral activity.”

The team now hope to study the predictive value of the rs34481144 in influenza patients in other countries.

Thomas concluded:  “A genetic marker of flu risk could make a life-saving difference, particularly during severe flu outbreaks, by helping prioritize high-risk patients for vaccination, drug therapy and other interventions. These results raise hopes that this newly identified IFITM3 variant might provide such a marker.”



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