Molecular basis for erythrocyte Le(a+ b+) and salivary ABH partial-secretor phenotypes: expression of a FUT2 secretor allele with an A-->T mutation at nucleotide 385 correlates with reduced alpha(1,2) fucosyltransferase activity.

The SewA385T mutation of the FUT2 gene was found to correlate with both the erthrocyte Le(a + b+) and/or salivary ABH partial-secretor phenotypes of Polynesians. Constructs with FUT1 and FUT2 wild type genes, and the FUT2 SewA385T, seG428A and seC571T mutated alleles, were cloned into pcDNAI, and expressed in COS-7 cells. COS-7 cells transfected with the SewA385T allele had weak, but detectable, alpha(1,2)fucosyltransferase activity, with an acceptor substrate pattern similar to the wild type FUT2 gene. Comparative kinetic studies from cell extracts with mutated SewA385T and wild type FUT2 alleles gave similar Km values, but less enzyme activity was present in cells transfected with SewA385T (Vmax 230 pmol h-1 mg-1), as compared to those transfected with FUT2 (Vmax 1030 pmol h-1 mg-1), suggesting that the mutated enzyme is more unstable. These results confirm that the molecular basis for the erythrocyte Le(a + b+), and the associated ABH salivary partial-secretor phenotype, is an amino acid change of Ile129-->Phe in the secretor alpha(1,2)fucosyltransferase.