title: Epidemiologic Association Between FUT2 Secretor Status and Severe Rotavirus Gastroenteritis in Children in the United States.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Multicenter 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.
  
  
  METHODS
  Paired 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
  Severe 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.
authors.affiliation: Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, US Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Payne
authors.affiliation: Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Currier
authors.affiliation: Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Mary A
authors.initials: MA
authors.lastname: Staat
authors.affiliation: Texas Children's Hospital, Houston.
authors.forename: Leila C
authors.initials: LC
authors.lastname: Sahni
authors.affiliation: Children's Mercy Hospitals and Clinics, Kansas City, Missouri.
authors.forename: Rangaraj
authors.initials: R
authors.lastname: Selvarangan
authors.affiliation: Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Natasha B
authors.initials: NB
authors.lastname: Halasa
authors.affiliation: Seattle Children's Hospital, Seattle, Washington.
authors.forename: Janet A
authors.initials: JA
authors.lastname: Englund
authors.affiliation: University of Rochester School of Medicine and Dentistry, Rochester, New York.
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Weinberg
authors.affiliation: Texas Children's Hospital, Houston8Baylor College of Medicine, Houston, Texas.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Boom
authors.affiliation: University of Rochester School of Medicine and Dentistry, Rochester, New York.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Szilagyi
authors.affiliation: Seattle Children's Hospital, Seattle, Washington.
authors.forename: Eileen J
authors.initials: EJ
authors.lastname: Klein
authors.affiliation: Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: James
authors.initials: J
authors.lastname: Chappell
authors.affiliation: Children's Mercy Hospitals and Clinics, Kansas City, Missouri.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Harrison
authors.affiliation: Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Barbara S
authors.initials: BS
authors.lastname: Davidson
authors.affiliation: Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, US Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: Slavica
authors.initials: S
authors.lastname: Mijatovic-Rustempasic
authors.affiliation: Children's Mercy Hospitals and Clinics, Kansas City, Missouri.
authors.forename: Mary D
authors.initials: MD
authors.lastname: Moffatt
authors.affiliation: Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Monica
authors.initials: M
authors.lastname: McNeal
authors.affiliation: Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, US Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: Mary
authors.initials: M
authors.lastname: Wikswo
authors.affiliation: Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, US Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Bowen
authors.affiliation: Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Ardythe L
authors.initials: AL
authors.lastname: Morrow
authors.affiliation: Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, US Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: Umesh D
authors.initials: UD
authors.lastname: Parashar
mesh_terms: D016022:Case-Control Studies; D002675:Child, Preschool; D005243:Feces / Q000821:virology; D005260:Female; D005647:Fucosyltransferases / Q000235:genetics*; D005759:Gastroenteritis / Q000453:epidemiology* / Q000235:genetics / Q000821:virology; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D011446:Prospective Studies; D012401:Rotavirus / Q000302:isolation & purification*; D012400:Rotavirus Infections / Q000453:epidemiology* / Q000235:genetics / Q000821:virology; D012463:Saliva / Q000821:virology; D014481:United States; D000097631:Galactoside 2-alpha-L-fucosyltransferase
chemical_list: D005647:Fucosyltransferases; D000097631:Galactoside 2-alpha-L-fucosyltransferase