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Original Investigation |

Epidemiologic Association Between FUT2 Secretor Status and Severe Rotavirus Gastroenteritis in Children in the United States

Daniel C. Payne, PhD, MSPH1; Rebecca L. Currier, PhD, MD2; Mary A. Staat, MD, MPH2; Leila C. Sahni, MPH3; Rangaraj Selvarangan, PhD4; Natasha B. Halasa, MD5; Janet A. Englund, MD6; Geoffrey A. Weinberg, MD7; Julie A. Boom, MD3,8; Peter G. Szilagyi, MD, MPH7; Eileen J. Klein, MD, MPH6; James Chappell, MD, PhD5; Christopher J. Harrison, MD4; Barbara S. Davidson, MPH2; Slavica Mijatovic-Rustempasic, MS1; Mary D. Moffatt, MD4; Monica McNeal, MS2; Mary Wikswo, MPH1; Michael D. Bowen, PhD1; Ardythe L. Morrow, PhD2; Umesh D. Parashar, MBBS, MPH1
[+] Author Affiliations
1Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, US Centers for Disease Control and Prevention, Atlanta, Georgia
2Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio
3Texas Children’s Hospital, Houston
4Children’s Mercy Hospitals and Clinics, Kansas City, Missouri
5Vanderbilt University Medical Center, Nashville, Tennessee
6Seattle Children’s Hospital, Seattle, Washington
7University of Rochester School of Medicine and Dentistry, Rochester, New York
8Baylor College of Medicine, Houston, Texas
JAMA Pediatr. 2015;169(11):1040-1045. doi:10.1001/jamapediatrics.2015.2002.
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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 Participants  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.

Main Outcomes and Measures  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 and Relevance  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.

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Distribution of Rotavirus Genotypes Among 188 Secretors
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