FUT2 non-secretor status is associated with altered susceptibility to symptomatic enterotoxigenic Escherichia coli infection in Bangladeshis

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.

Figure 1

rs601338-AA and rs200157007-TT SNPs are associated with non-secretors status and symptomatic ETEC infection. Association between the Lewis blood group phenotypes Le(a+b−) and Le(a−b+), symptomatic and asymptomatic ETEC infection in the children genotyped with (a) the rs601338-AA SNP and (b) the rs200157007-TT SNP. (c) Shows the combined datasets of the children found with the rs601338-AA and rs200157007-TT SNPs. The Fisher’s exact test was used to compare the relationship between children with the homozygous non-synonymous SNPs genotypes with symptomatic and asymptomatic ETEC infection and their Lewis blood group phenotypes.