Identification of a novel CYP2D6 allele associated with poor metabolism of sparteine in a Japanese population.
The relationship between genotypes associated with restriction fragment length polymorphisms at the P450 CYP2D locus and the metabolic phenotypes for sparteine in healthy Japanese subjects was investigated. Four distinct restriction fragments of 44 kb, 29 kb, 11.5 kb or 16 + 9 kb after digestion with Xba I were observed. The genotype of Xba I 11.5 kb, which is predictive of the poor metabolizer phenotype in Caucasians is also associated with Japanese poor metabolizers. Most Xba I 44 kb are associated with the extensive metabolizer phenotype. However, one Xba I 44 kb haplotype in linkage disequilibrium with a Bam HI restriction fragment length polymorphism allele, designated Bam HI 2.3 kb-, appears to be a novel mutant CYP2D6 allele in Japanese subjects having the poor metabolizer phenotype.
Department of Human Ecology, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan.
I
I
Kondo
M
M
Yonaha
K
K
Okano
F J
FJ
Gonzalez
I
I
Kanazawa
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics; D002648:Child; D019389:Cytochrome P-450 CYP2D6; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D005838:Genotype; D006801:Humans; D007564:Japan; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics* / Q000378:metabolism*; D010375:Pedigree; D010641:Phenotype; D012150:Polymorphism, Restriction Fragment Length; D013034:Sparteine / Q000378:metabolism*
D013034:Sparteine; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D019389:Cytochrome P-450 CYP2D6