The differential expression of the blood group P -A4GALT and P -A4GALT alleles is stimulated by the transcription factor early growth response 1.

BACKGROUNDThe P-1/P-2 phenotypic polymorphism is one of the earliest blood groups discovered in humans. These blood groups have been connected to different levels of expression of the A4GALT gene in P-1 and P-2 red blood cells; however, the detailed molecular genetic mechanism that leads to these two phenotypes has not been established. STUDY DESIGN AND METHODSAfter our previous identification of an association between the single-nucleotide polymorphisms (SNPs) rs2143918 and rs5751348 in A4GALT gene and the P-1/P-2 phenotype, we conduct a survey of transcription factors that might connect these SNPs with the differential expression of the P-1-A4GALT and P-2-A4GALT alleles. An in silico analysis of potential transcription factor binding motifs within the polymorphic SNPs rs2143918 and rs5751348 genomic regions was performed, and this was followed by reporter assays examining the candidate transcription factors, gene expression profiling, electrophoretic mobility shift assays, and P-1-A4GALT and P-2-A4GALT allelic expression analysis. RESULTSThe results revealed that the differential binding of transcription factor early growth response 1 to the SNP rs5751348 genomic region with the different genotypes in the A4GALT gene leads to differential activation of P-1-A4GALT and P-2-A4GALT expression. CONCLUSIONThe present investigation, together with our previous study (Lai et al., Transfusion 2014;54:3222-31), have elucidated the molecular genetic details associated with the P-1/P-2 blood groups.