Two previously proposed P(1)/P(2)-differentiating and nine novel polymorphisms at the A4GALT (P(k)) locus do not correlate with the presence of the P1 blood group antigen

BACKGROUND: The molecular genetics of the P blood group system and the absence of P1 antigen in the p phenotype are still enigmatic. One theory proposes that the same gene encodes for both the P1 and P(k )glycosyltransferases, but no polymorphisms in the coding region of the P(k )gene explain the P(1)/P(2 )phenotypes. We investigated the potential regulatory regions up- and downstream of the A4GALT (P(k)) gene exons. RESULTS: P(1 )(n = 18) and P(2 )(n = 9) samples from donors of mainly Swedish descent were analysed by direct sequencing of PCR-amplified 5'- and 3'-fragments surrounding the P(k )coding region. Seventy-eight P(1 )and P(2 )samples were investigated with PCR using allele-specific primers (ASP) for two polymorphisms previously proposed as P(2)-related genetic markers (-551_-550insC, -160A>G). Haplotype analysis of single nucleotide polymorphisms was also performed with PCR-ASP. In ~1.5 kbp of the 3'-untranslated region one new insertion and four new substitutions compared to a GenBank sequence (AL049757) were found. In addition to the polymorphisms at positions -550 and -160, one insertion, two deletions and one substitution were found in ~1.0 kbp of the 5'-upstream region. All 20 P(2 )samples investigated with PCR-ASP were homozygous for -550insC. However, so were 18 of the 58 P(1 )samples investigated. Both the 20 P(2 )and the 18 P(1 )samples were also homozygous for -160G. CONCLUSION: The proposed P(2)-specific polymorphisms, -551_-550insC and -160G, found in P(2 )samples in a Japanese study were found here in homozygous form in both P(1 )and P(2 )donors. Since P(2 )is the null allele in the P blood group system it is difficult to envision how these mutations would cause the P(2 )phenotype. None of the novel polymorphisms reported in this study correlated with P(1)/P(2 )status and the P1/p mystery remains unsolved.