Norovirus is a leading cause of viral gastroenteritis outbreaks worldwide. Histo-blood group antigens (HBGAs) are important host attachment factors in susceptibility to norovirus. In this study, the association of FUT2 gene, which participates in the biosynthesis of HBGAs, with norovirus infection has been investigated.
All relevant studies on the associations of FUT2 gene with norovirus were retrieved from PubMed, Web of Science, Embase, and Cochrane Library databases. Odds ratios (ORs) and 95% confidence interval (CI) were used to analyze the extracted data. I2 statistic, sensitivity analysis and publication bias analysis were used to confirm the findings. Subgroup analyses were performed for races, genotypes, development degree of the countries, publication years, age and setting when heterogeneity was recorded.
Twenty studies including 4066 participants were included for the meta-analysis. This analysis showed that there is a significant association between FUT2 gene and norovirus infection (OR = 3.02, 95%CI = 2.00-4.55, P < 0.001). Additionally, the ORs of norovirus infection among Chinese (OR = 4.49, 95%CI = 2.37-8.50, P < 0.001) were higher than those among Caucasian (OR = 3.23, 95%CI = 2.20-4.74, P < 0.001).
The meta-analysis suggested that FUT2 gene is associated with susceptibility to norovirus infection.

BACKGROUND: Norovirus and rotavirus are prominent enteric viruses responsible for severe acute gastroenteritis disease burden around the world. Both viruses recognize and bind to histo-blood group antigens, which are expressed by the fucosyltransferase 2 (FUT2) gene. Individuals with a functional FUT2 gene are termed \"secretors.\" FUT2 polymorphisms may influence viral binding patterns and, therefore, may influence host susceptibility to infection by these viruses.
METHODS: We performed a systematic review of the published literature on this topic. Data were abstracted and compiled for descriptive analyses and metaanalyses. We estimated pooled odds ratios (ORs) for infection using random-effects models.
RESULTS: We found that secretors were 9.9 times (95% confidence interval [CI], 3.9-24.8) as likely to be infected with genogroup II.4 noroviruses and 2.2 times as likely to be infected with genogroup II non-4 noroviruses (95% CI, 1.2-4.2) compared with nonsecretors. Secretors were also 26.6 times more susceptible to infections from P[8]-type rotaviruses compared with nonsecretors (95% CI, 8.3-85.0).
CONCLUSIONS: Our analyses indicate that host genetic susceptibility to norovirus and rotavirus infection may be strain specific. As strain distribution and the proportion of genetic phenotypes vary in different countries, future studies should focus on differences in susceptibility among various ethnicities. Knowledge of innate susceptibility to rotavirus and norovirus can lead to improved understanding of both vaccine performance and individual risk of disease.

Fucosyltransferase 2 (FUT2) mediates the inclusion of fucose in sugar moieties of glycoproteins and glycolipids. ABO blood group antigens and host-microbe interactions are influenced by FUT2 activity. About 20 % of the population has a \"non-secretor\" status caused by inactivating variants of FUT2 on both alleles. The non-sense mutation G428A and the missense mutation A385T are responsible for the vast majority of the non-secretor status in Caucasians, Africans, and Asians, respectively. Non-secretor individuals do not secrete fucose-positive antigens and lack fucosylation in epithelia. They also appear to be protected against a number of infectious diseases, such as Norovirus and Rotavirus infections. In recent years, genome-wide association studies (GWAS) identified inactivating variants at the FUT2 locus to be associated with primary sclerosing cholangitis (PSC), Crohn\'s disease (CD), and biochemical markers of biliary damage. These associations are intriguing given the important roles of fucosylated glycans in host-microbe interactions and membrane stability. Non-secretors have a reduced fecal content of Bifidobacteria. The intestinal bacterial composition of CD patients resembles the one of non-secretors, with an increase in Firmicutes and decreases in Proteobacteria and Actinobacteria. Non-secretor individuals lack fucosylated glycans at the surface of biliary epithelium and display a different bacterial composition of bile compared to secretors. Notably, an intact biliary epithelial glycocalix is relevant for a stable \'biliary HCO3 (-) umbrella\' to protect against toxic effects of hydrophobic bile salt monomers. Here, the biology of FUT2 will be discussed as well as hypotheses to explain the role of FUT2 in the pathophysiology of PSC and Crohn\'s disease.

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