Presence of nucleotide substitutions in transcriptional regulatory elements such as the erythroid cell‐specific enhancer‐like element and the ABO promoter in individuals with phenotypes A₃ and B₃, respectively

Abstract

Nucleotide substitutions in the transcriptional regulatory elements such as the +5.8-kb site and the ABO promoter appear to decrease transcription from the A- and B-alleles, resulting in reduction in A- and B-antigen expression in A3 and B3, respectively.

A novel mutation +5904 C>T of RUNX1 site in the erythroid cell‐specific regulatory element decreases the ABO antigen expression in Chinese population

“…firstly found the ABO regulation activity was dependent on the erythroid cell‐specific regulatory activity of +5·8 kb in intron 1 of ABO gene . Two binding sites for GATA transcription factors and one for RUNX1 were located close proximity to each other in the regulatory element . In the present study, we studied the characteristics of +5·8 kb site of the ABO subtype individuals with no mutation in the coding regions or splicing sites in China.…”

“…Besides the deletion of the +5·8 kb region, +5890T>G, +5893G>A, +5909A>G and a 23 bp deletion mutations on RUNX‐1 were also observed in the individuals with Bm and ABm in Japan . +5893 G>A and +5909 A>G were located in the 3′ adjacent to the GATA and RUNX site, respectively . Therefore, they could not bind their corresponding motifs nor impossible to affect the formation of enhancers containing GATA or RUNX1.…”

“…However, the deletion was not found in the individuals with ABO subtype in our study. Besides the deletion of the +5·8 kb region, +5890T>G, +5893G>A, +5909A>G and a 23 bp deletion mutations on RUNX‐1 were also observed in the individuals with Bm and ABm in Japan . +5893 G>A and +5909 A>G were located in the 3′ adjacent to the GATA and RUNX site, respectively .…”

“…It was found that most of the individuals with Bm phenotype were due to the deletion of the whole 5·8‐kb region in the Japanese . Furthermore, some mutations in the 5·8‐kb site were found in the individuals with ABO subtypes, including 23 bp deletion, 5890T>G, 5893G>A, and 5909A>G. These mutations could reduce the erythroid cell‐specific enhancer activity of the 5·8‐kb site and downregulate the transcription of A or B allele .…”

Effect on gene expression of three allelic variants in GATA motifs of ABO, RHD, and RHCE regulatory elements

“…However, allelic variants in the ABO Intron 1 enhancer element that cause reduced gene expression can present as mixed‐field A 3 or B 3 phenotypes . Possibly, cell‐to‐cell variation in the extent to which these variants impair transcription creates a spectrum of antigen densities detected as a continuum in flow cytometry histograms . RBC agglutination reactions, on the other hand, may require a minimum density to start and propagate.…”