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Impact of FUT2 Genotype on National Pediatric Population Burden of Norovirus-Associated Acute Gastroenteritis

Currier, Rebecca L
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1407407070

Abstract Details

2014, PhD, University of Cincinnati, Medicine: Epidemiology (Environmental Health).
BACKGROUND: Norovirus is a leading cause of acute gastroenteritis (AGE). Noroviruses bind histo-blood group antigens (HBGAs) on the gut surface, but only 70-80% of individuals have a functional copy of the FUT2 gene required for gut HBGA expression. We hypothesized that “secretors,” individuals with at least one active FUT2 allele, are more likely to be infected with norovirus than “non-secretors.” METHODS: From 12/2011 to 11/2012, active AGE surveillance was performed through the CDC New Vaccine Surveillance Network, comprised of six geographically representative U.S. pediatric sites. AGE cases were recruited from emergency departments and inpatient units; healthy controls were recruited at well-child visits. Salivary DNA was collected to determine FUT2 genotype and genetic ancestry. Stool specimens were tested for norovirus by realtime RT-PCR; positive samples were sequenced to determine norovirus genotype. RESULTS: Norovirus was detected in 302 (21%) of 1465 AGE cases and 52 (6%) of 826 healthy controls. Norovirus AGE cases were 2.78-fold more likely to be secretors vs. norovirus-free controls (p<0.001) in a logistic regression model which included race/ethnic background, age, study site, and health insurance. FUT2 secretors comprised all 155 cases and 21 asymptomatic infections positive for norovirus GII.4. Among norovirus-free controls, "at risk" FUT2 secretors were more common among Hispanics versus non-Hispanics (86% versus 74%, p = 0.004). CONCLUSIONS: FUT2 genotype is associated with norovirus infection risk and also varies with ethnicity and norovirus genotype. During 2011-2012 surveillance, the dominant circulating norovirus (GII.4) exclusively infected FUT2 secretors. These findings are important to the development of NoV vaccines. HBGAs produced by FUT2 biosynthesis enzymes may provide a therapeutic target.
Ardythe Morrow, Ph.D. (Committee Chair)
Sean Moore, M.S. M.D. (Committee Member)
Kim Dietrich, Ph.D. (Committee Member)
Mary Staat, M.D. (Committee Member)
Changchun Xie, Ph.D. (Committee Member)
142 p.
Epidemiology
norovirus; FUT2; acute gastroenteritis

Recommended Citations

Citations

  • Currier, R. L. (2014). Impact of FUT2 Genotype on National Pediatric Population Burden of Norovirus-Associated Acute Gastroenteritis [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1407407070

    APA Style (7th edition)

  • Currier, Rebecca. Impact of FUT2 Genotype on National Pediatric Population Burden of Norovirus-Associated Acute Gastroenteritis. 2014. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1407407070.

    MLA Style (8th edition)

  • Currier, Rebecca. "Impact of FUT2 Genotype on National Pediatric Population Burden of Norovirus-Associated Acute Gastroenteritis." Doctoral dissertation, University of Cincinnati, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1407407070

    Chicago Manual of Style (17th edition)

ucin1407407070
431
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This open access ETD is published by University of Cincinnati and OhioLINK.