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The Genetic Basis of NEC Susceptibility
Published in David J. Hackam, Necrotizing Enterocolitis, 2021
Lovya George, Wei Yu, Alain Cuna, Venkatesh Sampath
Polymorphisms in the FUT2 gene, which result in differing phenotypes of secreted fucosylated glycans on mucosa, have important implications in host–microbiome interactions. The FUT2 nonsecretor phenotype has been associated with alterations in the gut microbiome (66), with some studies demonstrating that it confers genetic susceptibility to Crohn disease (67). Morrow et al. (68) investigated the non-secretor status (AA) of the FUT2 polymorphism (428G→A) and found no evidence of association between this variant and NEC or surgical NEC. However, when salivary secretion of H-antigen was used to determine nonsecretor status, a positive association with NEC was found. Demmert et al. (69) investigated the same FUT2 polymorphism in a large prospective cohort of 2406 very low-birth-weight (VLBW) infants and found no association of this polymorphism with NEC. These differing results can possibly be explained by the varied influence of the FUT2 genotype on the secretor phenotype, which is also influenced by epigenetic changes and not always concordant with genotypes.
Familial Aggregation of Chronic Obstructive Pulmonary Disease
Published in Stephen D. Litwin, Genetic Determinants of Pulmonary Disease, 2020
Bernice H. Cohen, Gary A. Chase
In regard to genetic markers that might lead to familial aggregation, ABO type and secretor status could be involved. Preliminary observations suggested an ABO relationship in whites but not in blacks [25,26]. However, the findings have not been confirmed. Subsequent examination of ABH secretor status suggests that inability to secrete ABH substances into the body fluids may be an additional risk factor which interacts with ABO type. It is not clear at present whether such associations are real or spurious and what mechanisms are involved. That these apparent relationships may result secondarily from ethnic variation in susceptibility to COPD cannot be ruled out.
Carbohydrate Histochemistry
Published in Joan Gil, Models of Lung Disease, 2020
Bradley A. Schulte, Russell A. Harley, Samuel S. Spicer
Glycoprotein secretions in mouse mucous cells fail to show any terminal sugar other than sialic acid, except for the presence of fucose in about half the cells. In the rat, some mucous tubule cells contain terminal a-GalNAc, suggesting a similarity in structure to human blood group A antigen or the possible incomplete synthesis of oligosaccharides (Schulte and Spicer, 1983b). Human mucous tubules show differences correlated with the ABO blood group and perhaps with the secretor status of the donors. Thus, blood group A and AB specimens showed staining demonstrative of terminal α-GalNAc, (the terminal sugar in blood group A antigen), in contrast to the nonreactivity of blood group B and O specimens. Blood group B and AB specimens stain for the presence of terminal α-Gal, (the terminal residue in blood group B antigen), contrasting with the nonreactivity of blood group A and O specimens. These differences have since been confirmed using monoclonal antibodies against human ABH blood group antigens (unpublished observation).
Progress on norovirus vaccine research: public health considerations and future directions
Published in Expert Review of Vaccines, 2018
Claire P. Mattison, Cristina V. Cardemil, Aron J. Hall
Susceptibility to norovirus infection can vary based on an individual’s fucosyltransferase-2 (FUT2) gene. This gene regulates the expression of histo-blood group antigens (HBGAs), which serve as infection binding ligand on cells needed for infection [43]. Individuals with a functional FUT2 gene (‘secretors’) secrete HBGAs in their body fluid and express them on the epithelial cells in their gut and are more susceptible to norovirus GII.4 infection than those who are homozygous recessive for FUT2 (‘nonsecretors’) [44–47]. However, nonsecretors can still become infected with non-GII.4 norovirus strains, and being a nonsecretor only lowers, but does not eliminate, the risk of GII.4 norovirus infection [34,47]. Because of this genetic difference in susceptibility to norovirus infection and illness, it is important for vaccine trials and challenge studies to take into consideration individuals’ secretor status in their design; ultimately this will aid in better understanding of the impact of secretor status on vaccine efficacy.
FUT2 genotype and secretory status are not associated with fecal microbial composition and inferred function in healthy subjects
Published in Gut Microbes, 2018
Williams Turpin, Larbi Bedrani, Osvaldo Espin-Garcia, Wei Xu, Mark S. Silverberg, Michelle I. Smith, David S. Guttman, Anne Griffiths, Paul Moayyedi, Remo Panaccione, Hien Huynh, Hillary Steinhart, Guy Aumais, Konstantin Shestopaloff, Levinus A. Dieleman, Dan Turner, Andrew D. Paterson, Kenneth Croitoru
Analysis of bacterial taxa and OTUs were performed using two different filtering. The first analysis applied the filtering used in Tong et al.8 Briefly, to analyze at lower taxonomic levels, we filtered out low-abundant OTUs based on the criteria of minimum total observation count of 30 across all samples and being observed in at least 60% of the samples, reducing the total number of OTUs from 12,863 to 396.8 A second approach was then applied because filtering OTU that are observed in at least 60% of the samples had consequences on characterization of each individual's microbiota (Procrustes of OTU table with no filtering against OTU table filtered based on 60% of OTUs prevalence, M2 = 0.01, p-value <10−6) with some individuals having a biased microbiota profiles after applying this filtering (Supplementary Figure 1–2). Such approaches also decrease the number of comparison made. For such reason, we decided to apply less stringent criteria to filter OTUs that are observed in at least 5% of the samples and a minimum read count of 30 across all samples, leaving 4,353 OTUs (R software v2.14.1; http://CRAN.R-project.org). We then analysed bacterial composition based on OTUs grouped within the same taxonomic assignment at each level of bacterial taxonomy. A Bonferroni corrected p-value threshold of 0.05 was considered as significant (while 396 comparisons were performed at OTU level of bacterial taxonomy and 166 bacterial taxa). Raw p-values are reported. All genotype classes were compared in addition to secretor status and the p-value were corrected for intra-group compared.
Understanding the relationship between norovirus diversity and immunity
Published in Gut Microbes, 2021
Lauren A. Ford-Siltz, Kentaro Tohma, Gabriel I. Parra
A combination of both host genetic factors and immunological responses likely influences norovirus susceptibility, replication, and protection. One of the genetic factors contributing to norovirus susceptibility is the secretor status, which is associated with the presence of histo-blood group antigens (HBGAs) on the surface of epithelial cells. Although a definitive cellular receptor has not yet been identified for human noroviruses, HBGAs have been demonstrated to bind to the VP1 protein and facilitate attachment and/or entry into the cell (Figure 1, panel B).25–27