title: A systematic study of single-nucleotide polymorphisms in the A4GALT gene suggests a molecular genetic basis for the P1/P2 blood groups.
abstract: BACKGROUND
  The molecular mechanism for the formation of the P1/P2 blood groups remains unsolved. It has been shown that the P1/P2 polymorphism is connected to the different A4GALT gene expression levels in P1 and P2 red blood cells.
  
  
  METHODS
  The present investigation conducted a pilot investigation that involved the detailed and stepwise screening of single-nucleotide polymorphisms (SNPs) in the A4GALT gene, followed by a larger-scale association study. The transcription-inducing activity by the different genotypes of SNPs was analyzed using reporter assays.
  
  
  RESULTS
  A total of 416 different SNP sites in the A4GALT genes from four P1 and four P2 individuals were analyzed in the pilot investigation, and 11 SNP sites, distributed in the A4GALT Intron 1 region, exhibited an association with the P1/P2 phenotypes. In the follow-up association study, the genotypes at the 11 SNPs of a total of 338 individuals across four different ethnic populations were determined, and the results show that two SNPs, rs2143918 and rs5751348, are consistently associated with the P1/P2 phenotypes. Reporter assays demonstrated significantly higher transcription-inducing activity by the SNPs bearing the P(1)-allele genotype than by the SNPs bearing the P(2)-allele genotype and that the difference in transcriptional activity was determined by the different genotypes at SNP rs5751348.
  
  
  CONCLUSIONS
  The results of this investigation demonstrate a consistent association of A4GALT SNPs rs2143918 and rs5751348 with the P1/P2 phenotypes and suggest that SNP rs5751348 may lead to allelic variations in A4GALT gene expression and consequently leads to the formation of the P1/P2 phenotypes.
authors.affiliation: Institute of Biochemical Sciences, College of Life Science, National Taiwan University, Taipei, Taiwan; Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan; Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan; Blood Bank, Mackay Memorial Hospital, Taipei, Taiwan.
authors.forename: Yin-Ju
authors.initials: YJ
authors.lastname: Lai
authors.forename: Wan-Yi
authors.initials: WY
authors.lastname: Wu
authors.forename: Chen-Ming
authors.initials: CM
authors.lastname: Yang
authors.forename: Li-Rong
authors.initials: LR
authors.lastname: Yang
authors.forename: Chen-Chung
authors.initials: CC
authors.lastname: Chu
authors.forename: Yung-Syu
authors.initials: YS
authors.lastname: Chan
authors.forename: Marie
authors.initials: M
authors.lastname: Lin
authors.forename: Lung-Chih
authors.initials: LC
authors.lastname: Yu
mesh_terms: D000483:Alleles; D005260:Female; D005700:Galactosyltransferases / Q000096:biosynthesis / Q000235:genetics*; D005786:Gene Expression Regulation / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D010127:P Blood-Group System / Q000235:genetics* / Q000378:metabolism; D010865:Pilot Projects; D020641:Polymorphism, Single Nucleotide
chemical_list: D010127:P Blood-Group System; D005700:Galactosyltransferases; C045097:UDP-galactose-lactosylceramide alpha 1-4-galactosyltransferase