Single nucleotide polymorphisms in A4GALT spur extra products of the human Gb3/CD77 synthase and underlie the P1PK blood group system

PLoS One. 2018 Apr 30;13(4):e0196627. doi: 10.1371/journal.pone.0196627. eCollection 2018.

Abstract

Contrary to the mainstream blood group systems, P1PK continues to puzzle and generate controversies over its molecular background. The P1PK system comprises three glycosphingolipid antigens: Pk, P1 and NOR, all synthesised by a glycosyltransferase called Gb3/CD77 synthase. The Pk antigen is present in most individuals, whereas P1 frequency is lesser and varies regionally, thus underlying two common phenotypes: P1, if the P1 antigen is present, and P2, when P1 is absent. Null and NOR phenotypes are extremely rare. To date, several single nucleotide polymorphisms (SNPs) have been proposed to predict the P1/P2 status, but it has not been clear how important they are in general and in relation to each other, nor has it been clear how synthesis of NOR affects the P1 phenotype. Here, we quantitatively analysed the phenotypes and A4GALT transcription in relation to the previously proposed SNPs in a sample of 109 individuals, and addressed potential P1 antigen level confounders, most notably the red cell membrane cholesterol content. While all the SNPs were associated with the P1/P2 blood type and rs5751348 was the most reliable, we found large differences in P1 level within groups defined by their genotype and substantial intercohort overlaps, which shows that the P1PK blood group system still eludes full understanding.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies / chemistry
  • Blood Group Antigens / genetics*
  • Cholesterol / chemistry
  • Flow Cytometry
  • Galactosyltransferases / genetics*
  • Genotype
  • Globosides / genetics*
  • Glycosphingolipids / chemistry
  • Homozygote
  • Humans
  • Lipids / chemistry
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Real-Time Polymerase Chain Reaction

Substances

  • Antibodies
  • Blood Group Antigens
  • Globosides
  • Glycosphingolipids
  • Lipids
  • galactopyranosyl-1-4-paragloboside
  • Cholesterol
  • Galactosyltransferases
  • UDP-galactose-lactosylceramide alpha 1-4-galactosyltransferase

Grants and funding

This work was funded by National Science Centre of Poland Opus Project DEC-2014/13/B/NZ6/00227 (Prof. Marcin Czerwinski). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This publication was supported by the Wroclaw Centre of Biotechnology, programme The Leading National Research Centre (KNOW) for the years 2014-2018.