Studies on the genetic basis of Pk, P and P1 blood group antigen expression

University dissertation from Department of Laboratory Medicine, Lund University

Abstract: The clinically important carbohydrate P/GLOB blood group systems and collection give rise to both common (P1, P2) and rare (p, P1k, P2k) blood group phenotypes. The associated antibodies are implicated in severe transfusion reactions and recurrent spontaneous abortions. The aim of this study was to explore the molecular genetic basis of Pk, P and P1 antigen expression.

Sequence analysis of the A4GALT and B3GALNT1 genes proposed to synthesize the related Pk (Gb3) and P (Gb4) antigens, respectively, were performed in p and Pk individuals (n=99) of different geographic/ethnic origin. A total of 24 novel mutations were identified, emphasizing the genetic heterogeneity at the glycosyltransferase loci underlying these blood groups. As a result of this study, the P antigen was assigned its own blood group system, GLOB (028), by ISBT.

Expression studies in the Pk-negative Namalwa cells transfected with mutated A4GALT-constructs showed Pk expression levels comparable to negative controls. RBCs with p phenotype showed no Pk and P activity while both P and Pk expression on RBCs varied considerably between individuals with common phenotypes.

Sixteen polymorphic sites were detected while investigating if polymorphisms in the regulatory region of the A4GALT gene might be the basis for the P1/P2 phenotypes. No clear-cut correlation was found and two previously proposed P2-specific mutations were detected in homozygous form both in P1 and P2 donors indicating that these mutations are not the sole cause of the P1/P2 status. However, the correlation between the A4GALT locus and P2 status seems to be rather strong