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 ␣(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 (428G3A) in FUT2 segregated with complete resistance for the disease. Of all symptomatic individuals, 49% were homozygous (SeSe) and 51% heterozygous (Sese 428 ) secretors, and none were secretor negative (se 428 se 428 ), in contrast to 20% nonsecretors (se 428 se 428 ) among Swedish blood donors (n ؍ 104) (P < 0.0002) and 29% for asymptomatic individuals associated with nosocomial outbreaks (P < 0.00001). Furthermore, saliva from secretorpositive 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 (se 428 se 428 ) genotype is associated with resistance to nosocomial and sporadic outbreaks with norovirus.Noroviruses are the major cause of acute gastroenteritis worldwide among adults and are associated with the illness "winter vomiting disease," characterized by a short incubation period (24 to 48 h) and significant vomiting and diarrhea. While the viruses are highly contagious, with attack rates up to 70% (12), volunteer challenge studies have shown that a subset of individuals remain uninfected even after repeated challenges (2,20,26). At present, it is not clear why a fraction of individuals remain uninfected in norovirus outbreaks and why some volunteers are repeatedly resistant to experimental Norwalk virus inoculations. Recently, it was suggested that histo-blood group antigens and the secretor status might be associated with experimental Norwalk virus infections (4,10,11,16,17).The FUT2 gene, which is responsible for the secretor phenotype, encodes an ␣(1,2)-fucosyltransferase that regulates the expression of the ABH antigens in saliva and mucosal tissues and secretions. The FUT2 gene has a significant polymorphism with typical ethnic specificity (13). The nonsense mutation 428G3A (Trp1433stop) is characteristic for the dominating nonsecretor allele (se 428 ) in Europeans and appears in about 20% of the Caucasian population (13).The facts that about 20% of Europeans are nonsecretors and norovirus attack rates seldom exceeds 80% in a given outbreak led us to investigate, throughout a series of prospective studies, if the FUT2 secretor gene was associated with resistance to nosocomial and sporadic outbreaks caused by genogroup II (GGII) noroviruses, which dominate in all parts of the world (14).
MATERIALS AND METHODSSubjects and sampl...