Novel nonsynonymous single nucleotide polymorphisms in the CYP2D6 gene.

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Soyama A, Kubo T, Miyajima A, Saito Y, Shiseki K, Komamura K, Ueno K, Kamakura S, Kitakaze M, Tomoike H, Ozawa S, Sawada J

Novel nonsynonymous single nucleotide polymorphisms in the CYP2D6 gene.

Drug Metab Pharmacokinet. 2004 Aug;19(4):313-9.

PubMed ID

15499201 [ View in PubMed

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Abstract

Cytochrome P450 (CYP) 2D6 is an important drug-metabolizing enzyme, and its gene is known to be highly polymorphic. Here, we report five novel nonsynonymous single nucleotide polymorphisms (SNPs), and 65 other sequence variations detected from the gene coding for cytochrome P450 (CYP) 2D6 in 254 Japanese subjects. Two of the novel nonsynonymous SNPs were associated with the *10 key SNP, C100T. Among the 65 variations, 23 were novel, including 12 SNPs in 5'-flanking, 1 in 5'-untranslated, and 10 in intronic regions. The nonsynonymous SNPs in the CYP2D6 gene were as follows: 73 C>T (Arg25Trp, exon 1), 972 C>T (Ala90Val, exon 2), 1611 T>A (Phe120Ile, exon 3), 1720 A>C (Glu156Ala, exon 3), 3172 A>C (Glu334Ala, exon 7). The SNPs, 73C>T, 972 C>T, 1611 T>A, 1720 A>C and 3172 A>C were linked with *10, *1, *10, *1 and *2, respectively.

DrugBank Data that Cites this Article

Pharmaco-genomics

Drug	Interacting Gene/Enzyme	Allele name	Genotypes	Defining change(s)	Type(s)	Description	Details
Metoprolol	Cytochrome P450 2D6 Gene symbol: CYP2D6 UniProt: P10635	CYP2D6*47	Not Available	100C>T (rs1065852) -1426C>T -1235A>G show all 8 …	ADR Inferred	Increased risk of slow heart rate (bradycardia)	Details
Metoprolol	Cytochrome P450 2D6 Gene symbol: CYP2D6 UniProt: P10635	CYP2D6*51	Not Available	-1584C>G -1235A>G -740C>T show all 9 …	ADR Inferred	Increased risk of slow heart rate (bradycardia)	Details
Metoprolol	Cytochrome P450 2D6 Gene symbol: CYP2D6 UniProt: P10635	CYP2D6*57	Not Available	100C>T 310G>T 843T>G show all 10 …	ADR Inferred	Increased risk of slow heart rate (bradycardia)	Details
Venlafaxine	Cytochrome P450 2D6 Gene symbol: CYP2D6 UniProt: P10635	CYP2D6*47	Not Available	100C>T (rs1065852) -1426C>T -1235A>G show all 8 …	Effect Inferred	Poor drug metabolizer, lower dose requirements, nausea, vomiting and diarrhea	Details
Venlafaxine	Cytochrome P450 2D6 Gene symbol: CYP2D6 UniProt: P10635	CYP2D6*51	Not Available	-1584C>G -1235A>G -740C>T show all 9 …	Effect Inferred	Poor drug metabolizer, lower dose requirements, nausea, vomiting and diarrhea	Details
Venlafaxine	Cytochrome P450 2D6 Gene symbol: CYP2D6 UniProt: P10635	CYP2D6*57	Not Available	100C>T 310G>T 843T>G show all 10 …	Effect Inferred	Poor drug metabolizer, lower dose requirements, nausea, vomiting and diarrhea	Details
Codeine	Cytochrome P450 2D6 Gene symbol: CYP2D6 UniProt: P10635	CYP2D6*47	Not Available	100C>T (rs1065852) -1426C>T -1235A>G show all 8 …	Effect Inferred	Poor drug metabolizer, lower dose requirements	Details
Codeine	Cytochrome P450 2D6 Gene symbol: CYP2D6 UniProt: P10635	CYP2D6*51	Not Available	-1584C>G -1235A>G -740C>T show all 9 …	Effect Inferred	Poor drug metabolizer, lower dose requirements	Details
Codeine	Cytochrome P450 2D6 Gene symbol: CYP2D6 UniProt: P10635	CYP2D6*57	Not Available	100C>T 310G>T 843T>G show all 10 …	Effect Inferred	Poor drug metabolizer, lower dose requirements	Details
Amitriptyline	Cytochrome P450 2D6 Gene symbol: CYP2D6 UniProt: P10635	CYP2D6*47	Not Available	100C>T (rs1065852) -1426C>T -1235A>G show all 8 …	Effect Inferred	Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects	Details
Amitriptyline	Cytochrome P450 2D6 Gene symbol: CYP2D6 UniProt: P10635	CYP2D6*51	Not Available	-1584C>G -1235A>G -740C>T show all 9 …	Effect Inferred	Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects	Details
Amitriptyline	Cytochrome P450 2D6 Gene symbol: CYP2D6 UniProt: P10635	CYP2D6*57	Not Available	100C>T 310G>T 843T>G show all 10 …	Effect Inferred	Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects	Details
Imipramine	Cytochrome P450 2D6 Gene symbol: CYP2D6 UniProt: P10635	CYP2D6*47	Not Available	100C>T (rs1065852) -1426C>T -1235A>G show all 8 …	Effect Inferred	Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects	Details
Imipramine	Cytochrome P450 2D6 Gene symbol: CYP2D6 UniProt: P10635	CYP2D6*51	Not Available	-1584C>G -1235A>G -740C>T show all 9 …	Effect Inferred	Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects	Details
Imipramine	Cytochrome P450 2D6 Gene symbol: CYP2D6 UniProt: P10635	CYP2D6*57	Not Available	100C>T 310G>T 843T>G show all 10 …	Effect Inferred	Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects	Details
Dextromethorphan	Cytochrome P450 2D6 Gene symbol: CYP2D6 UniProt: P10635	CYP2D6*47	Not Available	100C>T (rs1065852) -1426C>T -1235A>G show all 8 …	Effect Inferred	Poor drug metabolizer, lower dose requirements	Details
Dextromethorphan	Cytochrome P450 2D6 Gene symbol: CYP2D6 UniProt: P10635	CYP2D6*51	Not Available	-1584C>G -1235A>G -740C>T show all 9 …	Effect Inferred	Poor drug metabolizer, lower dose requirements	Details
Dextromethorphan	Cytochrome P450 2D6 Gene symbol: CYP2D6 UniProt: P10635	CYP2D6*57	Not Available	100C>T 310G>T 843T>G show all 10 …	Effect Inferred	Poor drug metabolizer, lower dose requirements	Details
Nortriptyline	Cytochrome P450 2D6 Gene symbol: CYP2D6 UniProt: P10635	CYP2D6*47	Not Available	100C>T (rs1065852) -1426C>T -1235A>G show all 8 …	Effect Inferred	Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects	Details
Nortriptyline	Cytochrome P450 2D6 Gene symbol: CYP2D6 UniProt: P10635	CYP2D6*51	Not Available	-1584C>G -1235A>G -740C>T show all 9 …	Effect Inferred	Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects	Details
Nortriptyline	Cytochrome P450 2D6 Gene symbol: CYP2D6 UniProt: P10635	CYP2D6*57	Not Available	100C>T 310G>T 843T>G show all 10 …	Effect Inferred	Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects	Details
Tamoxifen	Cytochrome P450 2D6 Gene symbol: CYP2D6 UniProt: P10635	CYP2D6*47	Not Available	100C>T (rs1065852) -1426C>T -1235A>G show all 8 …	Effect Inferred	Poor response to drug treatment, shorter time to relapse	Details
Tamoxifen	Cytochrome P450 2D6 Gene symbol: CYP2D6 UniProt: P10635	CYP2D6*51	Not Available	-1584C>G -1235A>G -740C>T show all 9 …	Effect Inferred	Poor response to drug treatment, shorter time to relapse	Details
Tamoxifen	Cytochrome P450 2D6 Gene symbol: CYP2D6 UniProt: P10635	CYP2D6*57	Not Available	100C>T 310G>T 843T>G show all 10 …	Effect Inferred	Poor response to drug treatment, shorter time to relapse	Details
Desipramine	Cytochrome P450 2D6 Gene symbol: CYP2D6 UniProt: P10635	CYP2D6*47	Not Available	100C>T (rs1065852) -1426C>T -1235A>G show all 8 …	Effect Inferred	Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects	Details
Desipramine	Cytochrome P450 2D6 Gene symbol: CYP2D6 UniProt: P10635	CYP2D6*51	Not Available	-1584C>G -1235A>G -740C>T show all 9 …	Effect Inferred	Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects	Details
Desipramine	Cytochrome P450 2D6 Gene symbol: CYP2D6 UniProt: P10635	CYP2D6*57	Not Available	100C>T 310G>T 843T>G show all 10 …	Effect Inferred	Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects	Details
Clomipramine	Cytochrome P450 2D6 Gene symbol: CYP2D6 UniProt: P10635	CYP2D6*47	Not Available	100C>T (rs1065852) -1426C>T -1235A>G show all 8 …	Effect Inferred	Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects	Details
Clomipramine	Cytochrome P450 2D6 Gene symbol: CYP2D6 UniProt: P10635	CYP2D6*51	Not Available	-1584C>G -1235A>G -740C>T show all 9 …	Effect Inferred	Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects	Details
Clomipramine	Cytochrome P450 2D6 Gene symbol: CYP2D6 UniProt: P10635	CYP2D6*57	Not Available	100C>T 310G>T 843T>G show all 10 …	Effect Inferred	Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects	Details
Atomoxetine	Cytochrome P450 2D6 Gene symbol: CYP2D6 UniProt: P10635	CYP2D6*47	Not Available	100C>T (rs1065852) -1426C>T -1235A>G show all 8 …	Effect Inferred	Poor drug metabolizer, increased side effects.	Details
Atomoxetine	Cytochrome P450 2D6 Gene symbol: CYP2D6 UniProt: P10635	CYP2D6*51	Not Available	-1584C>G -1235A>G -740C>T show all 9 …	Effect Inferred	Poor drug metabolizer, increased side effects.	Details
Atomoxetine	Cytochrome P450 2D6 Gene symbol: CYP2D6 UniProt: P10635	CYP2D6*57	Not Available	100C>T 310G>T 843T>G show all 10 …	Effect Inferred	Poor drug metabolizer, increased side effects.	Details