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Molecular genetic analysis of the human Lewis histo-blood group system

, : Molecular genetic analysis of the human Lewis histo-blood group system. Journal of Biological Chemistry 269(46): 29271-8

The expression of Lewis histo-blood group antigen is determined by the Lewis type alpha(1,3/1,4) fucosyltransferase encoded in Fuc-TIII gene (Le gene) on chromosome 19. Weak hemagglutination reactions are often observed in the Lewis blood typing to cause false-negative reactions. The level of CA19-9 tumor marker, defined as sialylated Le(a) (sLe(a)), is influenced by the Lewis blood phenotype. The sLe(a) antigen is also considered to play a role in hematogenous metastasis of tumor cells. The accurate genotyping of Fuc-TIII gene would be, therefore, necessary for solving above questions. In addition to the two missense mutations previously reported by us, i.e. the T59G and the G508A, further sequence analyses revealed a new single base substitution, the T1067A, changing the Ile356 to Lys in the catalytic region. Polymerase chain reaction-restriction fragment length polymorphism methods were developed for the detection of these three missense mutations and applied in 15 Lewis negative (le/le) and 65 Lewis positive individuals (Le/Le or Le/le). These methods were found to be useful for genetic diagnosis for the Lewis histo-blood typing. All le alleles had the T59G mutation, whereas none of the Le alleles did. The le alleles were divided in two types, le1, having the G508A mutation, and le2, having the T1067A mutation. The T1067A mutation reduced the enzyme activity less than 10%, whereas the G508A mutation in the catalytic domain made the enzyme completely inactive. The frequency of occurrence of Le, le1, and le2 in the Japanese population by random sampling study was found to be 66, 30, and 4%, respectively.


PMID: 7961897

DOI: 10.1074/jbc.271.16.9830

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