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

Yokoi, Tsuyoshi; Kosaka, Yasuyuki; Chida, Michihiro; Chiba, Kazuhiro; Nakamura, Hidefumi; Ishizaki, Takashi; Kinoshita, Moritoshi; Sato, Kunio; Gonzalez, Frank J.; Kamataki, Tetsuya

doi:10.1097/00008571-199610000-00003

Cited by 49 publications

(32 citation statements)

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“…9,10 Despite an initial strong relationship between phenotype and genotype data in Asian populations, the observation of discordant cases has led to the identification of six rather rare new allelic variants (CYP2D6*14, *18, *21, *36x2, *39 and *44) that are associated with diminished or absent activity. 4,[11][12][13][14][15][16] In contrast, studies in Black populations describe probe drug dissociation and an overall reduced activity compared to Caucasians, also referred to as a 'right-shift' of the population phenotype distribution. This shift is similar to that seen in Asians.…”

Section: Introductionmentioning

confidence: 99%

Identification and characterization of novel sequence variations in the cytochrome P4502D6 (CYP2D6) gene in African Americans

et al. 2005

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Cytochrome P4502D6 (CYP2D6) genotyping reliably predicts poor metabolizer phenotype in Caucasians, but is less accurate in African Americans. To evaluate discordance we have observed in phenotype to genotype correlation studies, select African American subjects were chosen for complete resequencing of the CYP2D6 gene including 4.2 kb of the CYP2D7-2D6 intergenic region. Comparisons were made to a CYP2D6*1 reference sequence revealing novel SNPs in the upstream, coding and intervening sequences. These sequence variations, defining four functional alleles (CYP2D6*41B, *45A and B and *46), were characterized for their ability to influence splice site strength, transcription level or catalytic protein activity. Furthermore, their frequency was determined in a population of 251 African Americans. A À692 TGTG deletion (CYP2D6*45B) did not significantly decrease gene expression, nor could any other upstream SNP explain a genotype-discordant case. CYP2D6*45 and *46 have a combined frequency of 4% and can be identified by a common SNP. Carriers are predicted to exhibit an extensive or intermediate CYP2D6 phenotype.

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Section: Introductionmentioning

confidence: 99%

Identification and characterization of novel sequence variations in the cytochrome P4502D6 (CYP2D6) gene in African Americans

et al. 2005

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“…On the other hand, studies conducted by us and other groups have identified 21 variant alleles of the CYP2D6 gene in the Japanese population ( Fig. 1) (Yokoi et al, 1996;Chida et al, 1999;Nishida et al, 2000;Yamazaki et al, 2003;Soyama et al, 2004Soyama et al, , 2006Ebisawa et al, 2005). A number of these variant alleles have also been described in other Asian populations (Table 1).…”

mentioning

confidence: 89%

“…These results suggest that the relatively high activity of CYP2D6.14B may be attributed mainly to the absence of the P34S substitution. Yokoi et al (1996) have reported the kinetic parameters for CYP2D6.18-mediated bufuralol 1Ј-hydroxylation activity. The K m of CYP2D6.18 showed a 236-fold increase from the wild-type K m (990 M versus 4.2 M), a finding that is in agreement with the results we obtained in the COS-7 expression system.…”

Section: Functional Characterization Of Cyp2d6 Variantsmentioning

confidence: 99%

“…A number of these variant alleles have also been described in other Asian populations (Table 1). Among them,CYP2D6*4,CYP2D6*5,CYP2D6*14A,CYP2D6*18,CYP2D6*21,CYP2D6*36,and CYP2D6*44 are associated with the PM phenotype (Kagimoto et al, 1990;Gaedigk et al, 1991Gaedigk et al, , 2006Yokoi et al, 1996;Chida et al, 1999;Wang et al, 1999;Yamazaki et al, 2003). The catalytic properties of CYP2D6*10 and CYP2D6*2 have been studied extensively in vivo and in vitro using recombinant expression systems and reaction phenotyping.…”

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confidence: 99%

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Functional Characterization of 17CYP2D6Allelic Variants (CYP2D6.2, 10, 14A–B, 18, 27, 36, 39, 47–51, 53–55, and 57)

Sakuyama¹,

Sasaki²,

Ujiie³

et al. 2008

Drug Metab Dispos

141

122

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“…Specifically, the allele-defining CYP2D6*14 mutation (G1846A) was confirmed by MspI restriction digestion 31 and the CYP2D6*18 polymorphism was confirmed by a 9 bp length polymorphism assay. 32 In addition, all putative homozygous samples were rescreened for the CYP2D6*5 deletion using a separate, long PCR approach to amplify a 3.5 kb product diagnostic for the CYP2D6 gene deletion allele. 33 All PCR was performed on GeneAmp PCR System 9600 instrumentation (Applied Biosystems, Foster City, CA, USA) and PCR products were visualized by ethidium-bromide-stained 1% agarose gels.…”

Section: Recruitment Of Subjectsmentioning

confidence: 99%

Association between CYP2D6 genotype and tardive dyskinesia in Korean schizophrenics

Nikoloff

Fairchild

et al. 2002

Pharmacogenomics J

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The CYP2D6 gene codes for human cytochrome P450 2D6 enzyme, which is responsible for the metabolism of many psychiatric drugs. In schizophrenic patients treated with neuroleptics, decreased or loss of function CYP2D6 alleles may contribute to the development of tardive dyskinesia (TD), a movement disorder that frequently occurs with chronic neuroleptic treatment. The goal of this study was to determine whether the occurrence of TD is associated with CYP2D6 genotype in a cohort of Korean schizophrenics by employing a CYP450 GeneChip s oligonucleotide microarray and PCR assays to screen for 19 CYP2D6 alleles. Our results revealed that males with at least one decreased or loss of function allele have a moderately greater chance of developing TD than males with only wild-type alleles. Female schizophrenics did not have a significantly greater chance of developing TD. Our results demonstrate the utility of CYP2D6 microarrays to assess genotype status in this Korean cohort.

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

Cited by 49 publications

References 0 publications

Identification and characterization of novel sequence variations in the cytochrome P4502D6 (CYP2D6) gene in African Americans

Identification and characterization of novel sequence variations in the cytochrome P4502D6 (CYP2D6) gene in African Americans

Functional Characterization of 17CYP2D6Allelic Variants (CYP2D6.2, 10, 14A–B, 18, 27, 36, 39, 47–51, 53–55, and 57)

Association between CYP2D6 genotype and tardive dyskinesia in Korean schizophrenics

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