A new CYP2D6 allele with a nine base insertion in exon 9 in a Japanese population associated with poor metabolizer phenotype

作者：Yokoi T; Kosaka Y; Chida M; Chiba K; Nakamura H; Ishizaki T; Kinoshita M; Sato K; Gonzalez FJ; Kamataki T

来源：Pharmacogenetics, 1996, 6(5): 395-401.

DOI：10.1097/00008571-199610000-00003

• Xb alpha I RFLP
• yeast expression system
• population study
• bufuralol 1'-hydroxylase
• magnetic polymorphism

The CYP2D6 gene of a Japanese sparteine poor metabolizer (PM, proband) showing a urinary metabolic ratio of 31.6 was analysed, and a heterozygous CYP2D6(D), a deletional was found by restriction fragment length polymorphism analysis with Xba I enzyme, PM did not have any other previously described mutations in the CYP2D6 gene causing the loss of catalytic 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 CYP2D6(J9) and CPP2D6(D) alleles were to be inherited from the mother [2D6(W)/2D6(J9)] and the father [2D6(W)/2D6(D)], respectively. The 9-base insertion caused a large increase in the apparent K-m value for bufuralol 1'-hydroxylation as examined by expression of the enzyme protein in yeast, Four of 300 Japanese carried a heterozygous CYP2D6(J9) allele (0.7%, 4/600 chromosomes) as determined a polymerase chain reaction analysis.

• 出版日期1996-10