A NEW CYP2D6 ALLELE WITH A 9 BASE INSERTION IN EXON-9 IN A JAPANESE POPULATION ASSOCIATED WITH POOR METABOLIZER PHENOTYPE

The CYP2D6 gene of a Japanese sparteine poor metabolizer (PM, proband) showing a urinary metabolic ratio of 31.6 was analysed, and a heteroz ygous CYP2D6(D), a deletional was found by restriction fragment length polymorphism analysis with Xba I enzyme, PM did not have any other pr eviously described mutations in the CYP2D6 gene causing the loss of ca talytic activity of the CYP2D6 enzyme. Thus, a possible new allele(s) responsible the PM phenotype was analysed. The results indicated that the PM possessed a new 9-base in exon 9, designated CYP2D6(J9). The CY P2D6(J9) and CPP2D6(D) alleles were to be inherited from the mother [2 D6(W)/2D6(J9)] and the father [2D6(W)/2D6(D)], respectively. The 9-bas e insertion caused a large increase in the apparent K-m value for bufu ralol 1'-hydroxylation as examined by expression of the enzyme protein in yeast, Four of 300 Japanese carried a heterozygous CYP2D6(J9) alle le (0.7%, 4/600 chromosomes) as determined a polymerase chain reaction analysis.