Epidemiologic Association BetweenFUT2Secretor Status and Severe Rotavirus Gastroenteritis in Children in the United States

Abstract

IMPORTANCE A genetic polymorphism affecting FUT2 secretor status in approximately one-quarter of humans of European descent affects the expression of histo-blood group antigens on the mucosal epithelia of human respiratory, genitourinary, and digestive tracts. These histo-blood group antigens serve as host receptor sites necessary for attachment and infection of some pathogens, including norovirus.OBJECTIVE We investigated whether an association exists between FUT2 secretor status and laboratory-confirmed rotavirus infections in US children. DESIGN, SETTING, AND PARTICIPANTSMulticenter case-control observational study involving active surveillance at 6 US pediatric medical institutions in the inpatient and emergency department clinical settings. We enrolled 1564 children younger than 5 years with acute gastroenteritis (diarrhea and/or vomiting) and 818 healthy controls frequency matched by age and month, from December 1, 2011, through March 31, 2013. MAIN OUTCOMES AND MEASURESPaired fecal-saliva specimens were tested for rotavirus and for secretor status. Comparisons were made between rotavirus test-positive cases and healthy controls stratified by ethnicity and vaccination status. Adjusted multivariable analyses assessed the preventive association of secretor status against severe rotavirus gastroenteritis.RESULTS One (0.5%) of 189 rotavirus test-positive cases was a nonsecretor, compared with 188 (23%) of 818 healthy control participants (P < .001). Healthy control participants of Hispanic ethnicity were significantly less likely to be nonsecretors (13%) compared with healthy children who were not of Hispanic ethnicity (25%) (P < .001). After controlling for vaccination and other factors, children with the nonsecretor FUT2 polymorphism appeared statistically protected (98% [95% CI, 84%-100%]) against severe rotavirus gastroenteritis. CONCLUSIONS AND RELEVANCESevere rotavirus gastroenteritis was virtually absent among US children who had a genetic polymorphism that inactivates FUT2 expression on the intestinal epithelium. We observed a strong epidemiologic association among children with rotavirus gastroenteritis compared with healthy control participants. The exact cellular mechanism behind this epidemiologic association remains unclear, but evidence suggests that it may be rotavirus genotype specific. The lower prevalence of nonsecretors among Hispanic children may translate to an enhanced burden of rotavirus gastroenteritis among this group. Our findings may have bearing on our full understanding of rotavirus infections and the effects of vaccination in diverse populations.

Human Genetic Determinants of Viral Diseases

“…However, the protective effects of altered FUT2 alleles may be norovirus strain specific (46), and additional related factors, such as ABO blood type, also influence susceptibility (63, 96, 107). In addition, FUT2 functionality has been linked to infection with rotavirus, another enteric pathogen that causes diarrheal disease in children, and that utilizes cell surface carbohydrates for attachment (114). These results provide a basis for identifying individuals resistant to infection by these viruses and suggest that the development of purified fucose-containing oligosaccharides may be effective as anti-infectives (163).…”

Shedding of porcine circovirus type 1 DNA and rotavirus RNA by infants vaccinated with Rotarix®

“…Of the 12 in the latter group, 5 had no Rotarix Ò RVA RNA detected on day 3, 2 had none detected on day 5, and 2 had none detected on days 3 and 5. Using the highest copy number detected for each of the 21 infants on day 3, the median value was 5.2£10 6 copies/mL (IQR 1.4£10 5 to 1.0£10 8 ; range 377 to 1.3£10 10 ) Among the 7 infants with Rotarix Ò RVA RNA detected on day»30, the median copy number was 1.2£10 5 /mL. On day »45, the 3 subjects with Rotarix Ò RVA RNA detected had 2.4£10 3 , 6.4£10 3 , and 1.5£10 5 copies/mL.…”

“…Interestingly, this is the approximate proportion (25-26%) of non-Hispanic US infants found in a control group to be FUT2 (a [1,2] fucosyltransferase 2) nonsecretors. 8,9 FUT2 nonsecretors may be protected against infection with P[8] rotavirus such as the vaccine virus contained in Rotarix Ò . 8,10-12 However, we did not perform serologic assessments to more fully determine which infants likely had "vaccine-take," and, as described earlier, the duration of shedding from just passive transit of vaccine virus is not known.…”

Rotavirus infection and histo-blood group antigens in the children hospitalized with diarrhoea in China

“…Certainly, strict case and control studies are necessary to address this issue clearly. In addition, the recent case-control observational study investigating the association between FUT2 status and RV infections in US children found that non-secretor children appeared statistically protected against severe rotavirus gastroenteritis [12].…”