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Weak blood group B phenotypes may be caused by variations in the CCAAT‐binding factor/NF‐Y enhancer region of the ABO gene
Author(s) -
Seltsam Axel,
Wagner Franz F.,
Grüger Daniela,
Gupta Christa D.,
BadeDoeding Christina,
Blasczyk Rainer
Publication year - 2007
Publication title -
transfusion
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.045
H-Index - 132
eISSN - 1537-2995
pISSN - 0041-1132
DOI - 10.1111/j.1537-2995.2007.01475.x
Subject(s) - abo blood group system , enhancer , biology , allele , gene , microbiology and biotechnology , genetics , transcription factor
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.