FUT2 genetic variants as predictors of tumor development with hepatocellular carcinoma

Abstract

Lewis antigens related to the ABO blood group are fucosylated oligosaccharides and are synthesized by specific glycosyltransferases (FUTs). FUTs are involved in various biological processes including cell adhesion and tumor progression. The fucosyltransferase-2 gene (FUT2) encodes alpha (1,2) fucosyltransferase, which is responsible for the addition of the alpha (1,2)-linkage of fucose to glycans. Aberrant fucosylation occurs frequently during the development and progression of hepatocellular carcinoma (HCC). However, the association of FUT2 polymorphisms with HCC development has not been studied. Therefore, we aimed to investigate the association of FUT2 polymorphisms with demographic, etiological, and clinical characteristics and with susceptibility to HCC. In this study, a total of 339 patients and 720 controls were recruited. The genotypes of FUT2 at four single-nucleotide polymorphisms (SNPs; rs281377, rs1047781, rs601338, and rs602662) were detected by real-time polymerase chain reaction from these samples. Compared with the wild-type genotype at SNP rs1047781, which is homozygous for nucleotides AA, at least one polymorphic T allele (AT or TT) displayed significant association with clinical stage (p = 0.048) and tumor size (p = 0.022). Our study strongly implicates the polymorphic locus rs1047781 of FUT2 as being associated with HCC development.

The contribution of common and rare genetic variants to variation in metabolic traits in 288,137 East Asians

“…Previously, Chambers et al reported that a synonymous variant (rs281377) and an intronic variant (rs516246) in FUT2 were associated with alkaline phosphatase (ALP) and γ-glutamyl transferase (GGT), respectively 4 . The coding rs1047781 variant has been reported to display a marginally significant association with an indicator of liver damage (AST/ALT ratio), but the association with absolute levels of AST or ALT is novel 39 . In mice, abrogation of Fut2 –/– function leads to acute liver damage and increased alkaline phosphatase, AST, and ALT levels 38 .…”