Abstract
Polymorphisms of the FUT2 gene alters glycan ABO(H) blood group and Lewis antigen expression (commonly known as non-secretor status) in the small intestinal mucosa. Whilst non-secretor status affects 20% of the population worldwide, it has been reported to be present in up to 40% of all Bangladeshis. Furthermore, Bangladeshi children are reportedly more susceptible to symptomatic enterotoxigenic Escherichia coli (ETEC) infection if they are non-secretors. Therefore, in an attempt to identify a non-secretor status genotypic biomarker of altered susceptibility to ETEC infection, we used the 1000 Genomes Project to identify three population related non-synonymous FUT2 single nucleotide polymorphisms (SNPs). We then assessed the genotypic frequency of these SNPs in Bangladeshi children who had been clinically monitored for ETEC infection. One novel missense FUT2 SNP, rs200157007-TT and the earlier established rs601338-AA SNP were shown to be causing non-secretor status, with these SNPs being associated with symptomatic but not asymptomatic ETEC infection. Moreover, rs200157007-TT and rs601338-AA were associated with symptomatic but not asymptomatic ETEC infection irrespective of the child’s Lewis secretor status, suggesting FUT2, the regulator of Lewis and ABO(H) antigens in the intestinal mucosa, could be a host genotypic feature affecting susceptibility to ETEC infection.
Highlights
Polymorphisms of the FUT2 gene alters glycan ABO(H) blood group and Lewis antigen expression in the small intestinal mucosa
Out of the initial 40 FUT2 single nucleotide polymorphisms (SNPs) we identified in the Bangladeshi 1000 Genomes Project dataset, three were non-synonymous (Table 1) and were predicted to change the amino acid sequence
To identify a potential non-secretor status genetic biomarker in the Bangladeshi population, that is associated with the severity of enterotoxigenic Escherichia coli (ETEC) infection[2,4,5], we used the 1000 Genomes Project dataset[16] to identify three potential FUT2 SNP candidates that could cause non-secretor status in Bangladeshi individuals
Summary
Polymorphisms of the FUT2 gene alters glycan ABO(H) blood group and Lewis antigen expression (commonly known as non-secretor status) in the small intestinal mucosa. Rs200157007-TT and rs601338-AA were associated with symptomatic but not asymptomatic ETEC infection irrespective of the child’s Lewis secretor status, suggesting FUT2, the regulator of Lewis and ABO(H) antigens in the intestinal mucosa, could be a host genotypic feature affecting susceptibility to ETEC infection. Mutations in both FUT3 alleles can occur These individuals are classified as Lewis negative (Le(a−b−) phenotype) irrespective of their FUT2 secretor status[2]. Bangladeshi children with the Lewis non-secretor Le(a+b−) phenotype were found to have an increased susceptibility to symptomatic infection caused by enterotoxigenic Escherichia coli (ETEC) expressing the colonisation factor antigen I (CFA/I) fimbriae, as well as other related CFA/I ETEC fimbriae such as CS1, CS2, CS4, CS14, CS17, CS195. In East Asia, non-secretor status is caused by a FUT2 missense mutation known as rs1047781A > T (A385T, IIe129Phe, Table 1) and has been shown to confer susceptibility similar to diseases as the rs601338G > A genotype[14,15]
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