FUT2 secretor status influences rotavirus gastroenteritis susceptibility

Last Updated: 2015-09-21

By Will Boggs MD

NEW YORK (Reuters Health) - FUT2 gene secretor status influences whether or not children are susceptible to severe rotavirus gastroenteritis, researchers report.

"Overall, these findings offer a more complete epidemiological understanding of rotavirus infection susceptibility and prevention," Dr. Daniel C. Payne, from the Centers for Disease Control and Prevention, Atlanta, told Reuters Health by email.

"An association between host genetics and pathogen infection may be one important part of the puzzle in explaining why some population differences have been observed in rotavirus disease burden, how the vaccines perform in certain populations, and perhaps why some strains of rotavirus are more prevalent among particular populations," he said.

Genetic polymorphisms that affect the expression of alpha(1,2)-fucosyltransferase 2 (FUT2) and other enzymes have been shown to influence susceptibility to several infections, but their association with rotavirus infections is uncertain.

Dr. Payne's team investigated whether FUT2 secretor/nonsecretor status was associated with laboratory-confirmed rotavirus infections in their study of 1564 children younger than 5 years with acute gastroenteritis and 818 healthy controls.

One hundred eighty-nine patients tested positive for rotavirus, compared with none of the healthy controls, according to the September 21 JAMA Pediatrics online report.

All but one of the rotavirus-positive patients were characterized as FUT2 secretors, compared with 630 (77%) of the healthy controls.

When stratifying the children by rotavirus vaccine status, nonsecretors made up 1% of the rotavirus-positive vaccinees compared with 18% of the rotavirus-negative vaccinees.

In multivariable analysis, nonsecretor FUT2 polymorphism was associated with 98% protection against hospitalized and emergency department-attended rotavirus gastroenteritis. By comparison, rotavirus vaccine appeared to be 77% effective.

"While similar epidemiologic findings had been recently reported from children on four continents, we were still surprised at the strength of this association in U.S. children," Dr. Payne said. "Severe rotavirus gastroenteritis was virtually absent among U.S. children having a genetic polymorphism that inactivates FUT2 expression on the intestinal epithelium."

"We found that fewer U.S. Hispanic children (compared with non-Hispanic children) lacked the genetic polymorphism associated with preventing rotavirus infections, and it can be inferred that U.S. Hispanics may be at higher risk from this disease compared with their non-Hispanic counterparts," Dr. Payne added.

He concluded, "There is a great deal more still to learn about why some children appear to be innately susceptible to certain viruses and others do not. But what we do know from extensive study is that the incidence of rotavirus gastroenteritis has dramatically decreased in the U.S. since the licensure of both rotavirus vaccines, and we continue to observe high vaccine effectiveness in all U.S. populations that have been evaluated."

Dr. Kari Debbink, from the University of Michigan, Ann Arbor, told Reuters Health Health by email, "Previous work in other populations has demonstrated a link between rotavirus susceptibility and the secretor-negative phenotype. This phenomenon is seen in norovirus as well, which also utilizes histoblood group antigens as putative receptors."

"One person with a nonsecretor phenotype contracted rotavirus in this study," Dr. Debbink said. "This demonstrates that there are some rotavirus genotypes that are able to infect nonsecretors, so this phenotype is not 100% protective. More research on which rotavirus genotypes are able to infect nonsecretors is warranted, as this may be an important consideration in future vaccine formulations if any of these genotypes are or become common in the general population."

Dr. Jacques Le Pendu from the University of Nantes, France, recently reported the association between FUT2 polymorphisms and resistance to rotavirus infection. He told Reuters Health by email, "The finding might contribute to explain why vaccines are so efficient in developed countries, but much less so in some developing countries. Since rotavirus vaccines are live vaccines, infection is required for efficacy. Genetically resistant children may not be infected (or only poorly) by the vaccine strains and therefore may not be well immunized."

"Since frequencies of either FUT2- or FUT3-null individuals are variable across populations, a combination of high FUT2/FUT3 null frequency with circulation of strains able to infect these people would result in a failure of the vaccine to decrease the rotavirus burden," Dr. Le Pendu suggested.

"This remains quite speculative at this point but provides a potential explanation for the important differential efficacy of the vaccines in different geographic areas and their distressing failure in some of the countries where they are most needed. If correct, that should lead to modifications of the vaccines composition for better efficacy regardless of the human genetics and virus diversity," he added.

The National Institutes of Health partially supported this research. One coauthor reported receiving research support from GlaxoSmithKline.

SOURCE: http://bit.ly/1LruXpL

JAMA Pediatr 2015.