One novel single nucleotide polymorphism c.424A>G on A1.02 allele in ABO glycosyltransferases leads to Aweak phenotype

Background The dysfunction of the ABO glycosyltransferase (GT) enzyme, which is caused by mutations in the ABO gene, can lead to weak ABO phenotypes. In this study, we have discovered a novel weak ABO subgroup allele and investigated the underlying mechanism to causing its Aweak phenotype. Materials and methods The ABO phenotyping and genotyping were performed by serological studies and direct DNA sequencing of ABO gene. The role of the novel single nucleotide polymorphism (SNP) was evaluated by 3D model, predicting protein structure changes, and in vitro expression assay. The total glycosyltransferase transfer capacity in supernatant of transfected cells was examined. Results The results of serological showed the subject was Aweak phenotype. A novel SNP c.424A > G (p. M142V) based on ABO*A1.02 was identified, and the genotype of the subject was AW-var/O.01 according to the gene analysis. In silico analysis showed that the SNP c.424A > G on the A allele may change the local conformation by damaging the hydrogen bonds and reduce the stability of GT. In vitro expression study showed that SNP p.M142V impaired H to A antigen conversion, although it did not affect the generation of A glycosyltransferase (GTA). Conclusions One novel AW allele was identified and the SNP c.424A > G (p.M142V) can cause the Aweak phenotype through damaging the hydrogen bonds and reducing stability of the GTA.