Weak blood group B phenotypes may be caused by variations in the CCAAT-binding factor/NF-Y enhancer region of the ABO gene

Transfusion. 2007 Dec;47(12):2330-5. doi: 10.1111/j.1537-2995.2007.01475.x. Epub 2007 Aug 30.


Background: Binding of CCAAT-binding factor NF-Y (CBF/NF-Y) to a 43-bp repeat unit in the minisatellite region in the 5' region of the ABO gene (CBF/NF-Y enhancer region) plays an important role in regulating the transcription of ABO genes. The common ABO alleles were found to have CBF/NF-Y enhancer regions with specific numbers of 43-bp minisatellite repeats.

Material and methods: Blood samples from four healthy blood donors with weak B phenotypes were subjected to extensive ABO genotyping, including nucleotide sequencing of the 5' regulatory region containing the CBF/NF-Y enhancer.

Results: The coding region of the ABO genes exhibited common ABO*B101-heterozygous genotypes in all samples, but unexpected variations were observed in the CBF/NF-Y enhancer region. In two cases, the CBF/NF-Y enhancer motifs did not exhibit the expected ABO allele dependency. One, an AB(weak) sample was heterozygous for ABO*A101 and ABO*B101 but homozygous for the ABO*B101-specific CBF/NF-Y motif. The second had a common ABO*B101/ABO*O01 genotype but was heterozygous for ABO*A101- and ABO*O01-specific enhancer motifs. In the other two samples, novel CBF/NF-Y motifs were found. One contained a shortened version of an otherwise ABO*B101-specific CBF/NF-Y motif, and the other had a single-base substitution located 12 bp upstream from the beginning of the first 43-bp repeat of an ABO*B101-specific CBF/NF-Y enhancer sequence.

Conclusion: The frequency of variations in the CBF/NF-Y region of the ABO gene in these samples with presumably common ABO*B101 alleles suggests that weak blood group B phenotypes may be caused by sequence variations in the CBF/NF-Y regulatory region.

MeSH terms

  • ABO Blood-Group System / genetics*
  • Alleles
  • CCAAT-Binding Factor / metabolism*
  • Enhancer Elements, Genetic / genetics*
  • Genotype
  • Humans
  • Mutation
  • Phenotype
  • Protein Binding
  • Regulatory Sequences, Nucleic Acid / genetics


  • ABO Blood-Group System
  • CCAAT-Binding Factor