title: A homozygous nonsense mutation (428G-->A) in the human secretor (FUT2) gene provides resistance to symptomatic norovirus (GGII) infections.
abstract: Noroviruses (formerly Norwalk-like viruses) are a major cause of acute gastroenteritis worldwide and are associated with a significant number of nosocomial and food-borne outbreaks. In this study we show that the human secretor FUT2 gene, which codes for an alpha(1,2)-fucosyltransferase synthesizing the H-type 1 antigen in saliva and mucosa, is associated with susceptibility to norovirus infections. Allelic polymorphism characterization at nucleotide 428 for symptomatic (n = 53) and asymptomatic (n = 62) individuals associated with nosocomial and sporadic norovirus outbreaks revealed that homozygous nonsense mutation (428G-->A) in FUT2 segregated with complete resistance for the disease. Of all symptomatic individuals, 49% were homozygous (SeSe) and 51% heterozygous (Sese428) secretors, and none were secretor negative (se428se428), in contrast to 20% nonsecretors (se428se428) among Swedish blood donors (n = 104) (P < 0.0002) and 29% for asymptomatic individuals associated with nosocomial outbreaks (P < 0.00001). Furthermore, saliva from secretor-positive and symptomatic patients but not from secretor-negative and asymptomatic individuals bound the norovirus strain responsible for that particular outbreak. This is the first report showing that the FUT2 nonsecretor (se428se428) genotype is associated with resistance to nosocomial and sporadic outbreaks with norovirus.
authors.affiliation: Department of Virology, Swedish Institute for Infectious Disease Control, Solna, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Thorven
authors.forename: Ammi
authors.initials: A
authors.lastname: Grahn
authors.forename: Kjell-Olof
authors.initials: KO
authors.lastname: Hedlund
authors.forename: Hugo
authors.initials: H
authors.lastname: Johansson
authors.forename: Christer
authors.initials: C
authors.lastname: Wahlfrid
authors.forename: Göran
authors.initials: G
authors.lastname: Larson
authors.forename: Lennart
authors.initials: L
authors.lastname: Svensson
mesh_terms: D017250:Caliciviridae Infections / Q000097:blood / Q000453:epidemiology / Q000235:genetics / Q000503:physiopathology*; D018389:Codon, Nonsense; D004196:Disease Outbreaks; D004198:Disease Susceptibility / Q000097:blood; D005243:Feces / Q000821:virology; D005647:Fucosyltransferases / Q000235:genetics / Q000502:physiology*; D005759:Gastroenteritis / Q000097:blood / Q000503:physiopathology / Q000821:virology; D006720:Homozygote; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D029322:Norovirus / Q000472:pathogenicity / Q000502:physiology*; D012463:Saliva / Q000821:virology; D000097631:Galactoside 2-alpha-L-fucosyltransferase
chemical_list: D018389:Codon, Nonsense; D005647:Fucosyltransferases; D000097631:Galactoside 2-alpha-L-fucosyltransferase