Sequence variation in the 5' untranslated region of the human A4GALT gene is associated with, but does not define, the P1 blood-group polymorphism.

The gene responsible for the P1 polymorphism of the P blood-group system remains unidentified, although the A4GALT gene, whose product is responsible for the production of P(k), has been implicated. No coding differences in A4GALT account for the P1 polymorphism, but homozygosity for two polymorphisms (-551_-550insC and -160A>G) in the 5' untranslated region of the gene has been reported to be unique to Japanese P1- individuals. This study aimed to confirm this correlation in a larger number of British individuals.,Serologically confirmed P1+ (n = 35) and P1- (n = 15) individuals were genotyped for polymorphisms in the 5' untranslated region of A4GALT.,In addition to those previously reported, a further polymorphism, -164C>T, was identified. All P1- individuals were homozygous for -551_-550insC and -160G as compared with 10 of 35 (29%) P1+ individuals (P = 0.000003, two-tailed Fisher's exact test). Allele frequencies for all polymorphisms and estimated haplotype frequencies across the region differed significantly between P1+ and P1- groups.,Homozygosity for the A4GALT-551_-550insC and -160G allele is significantly associated with, but not restricted to, the P1- phenotype. No single A4GALT genotype or haplotype was unique to P1- individuals. Thus, A4GALT cannot be unequivocally confirmed as the gene responsible for the P1 phenotype.