CYP2D6 phenotype-genotype relationships in African-Americans and Caucasians in Los Angeles.

Article Details

Citation

Copy to clipboard

Leathart JB, London SJ, Steward A, Adams JD, Idle JR, Daly AK

CYP2D6 phenotype-genotype relationships in African-Americans and Caucasians in Los Angeles.

Pharmacogenetics. 1998 Dec;8(6):529-41.

PubMed ID

9918137 [ View in PubMed

]

Abstract

CYP2D6 genotyping (CYP2D6*3, CYP2D6*4, CYP2D6*5, CYP2D6*13, CYP2D6*16 alleles and gene duplications) was previously performed on 1053 Caucasian and African-American lung cancer cases and control individuals and no significant difference in allele frequencies between cases and control individuals detected. We have carried out additional genotyping (CYP2D6*6, CYP2D6*7, CYP2D6*8, CYP2D6*9, CYP2D6*10, CYP2D6*17 alleles) and debrisoquine phenotyping on subgroups from this study to assess phenotype-genotype relationships. African-Americans showed significant differences from Caucasians with respect to frequency of defective CYP2D6 alleles, particularly CYP2D6*4 and CYP2D6*5. The CYP2D6*17 allele occurred at a frequency of 0.26 among 87 African-Americans and appeared to explain higher average metabolic ratios among African-Americans compared with Caucasians. CYP2D6*6, CYP2D6*8, CYP2D6*9 and CYP2D6*10 were rare in both ethnic groups but explained approximately 40% of higher than expected metabolic ratios among extensive metabolizers. Among individuals phenotyped with debrisoquine, 32 out of 359 were in the poor metabolizer range with 24 of these (75%) also showing two defective CYP2D6 alleles. Additional single strand conformational polymorphism analysis screening of samples showing large phenotype-genotype discrepancies resulted in the detection of three novel polymorphisms. If subjects taking potentially interfering drugs were excluded, this additional screening enabled the positive identification of 88% of phenotypic poor metabolizers by genotyping. This sensitivity was comparable with that of phenotyping, which identified 90% of those with two defective alleles as poor metabolizers.

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*36	Not Available	100C>T (rs1065852) -1426C>T variable number of A’s in the region -1258 to -1237a show all 9 …	ADR Inferred	Increased risk of slow heart rate (bradycardia)	Details
Metoprolol	Cytochrome P450 2D6 Gene symbol: CYP2D6 UniProt: P10635	CYP2D6*38	Not Available	2587_2590delGACT (rs72549351)	ADR Inferred	Increased risk of slow heart rate (bradycardia)	Details
Venlafaxine	Cytochrome P450 2D6 Gene symbol: CYP2D6 UniProt: P10635	CYP2D6*36	Not Available	100C>T (rs1065852) -1426C>T variable number of A’s in the region -1258 to -1237a 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*38	Not Available	2587_2590delGACT (rs72549351)	Effect Inferred	Poor drug metabolizer, lower dose requirements, nausea, vomiting and diarrhea	Details
Codeine	Cytochrome P450 2D6 Gene symbol: CYP2D6 UniProt: P10635	CYP2D6*36	Not Available	100C>T (rs1065852) -1426C>T variable number of A’s in the region -1258 to -1237a show all 9 …	Effect Inferred	Poor drug metabolizer, lower dose requirements	Details
Codeine	Cytochrome P450 2D6 Gene symbol: CYP2D6 UniProt: P10635	CYP2D6*38	Not Available	2587_2590delGACT (rs72549351)	Effect Inferred	Poor drug metabolizer, lower dose requirements	Details
Amitriptyline	Cytochrome P450 2D6 Gene symbol: CYP2D6 UniProt: P10635	CYP2D6*36	Not Available	100C>T (rs1065852) -1426C>T variable number of A’s in the region -1258 to -1237a 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*38	Not Available	2587_2590delGACT (rs72549351)	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*36	Not Available	100C>T (rs1065852) -1426C>T variable number of A’s in the region -1258 to -1237a 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*38	Not Available	2587_2590delGACT (rs72549351)	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*36	Not Available	100C>T (rs1065852) -1426C>T variable number of A’s in the region -1258 to -1237a show all 9 …	Effect Inferred	Poor drug metabolizer, lower dose requirements	Details
Dextromethorphan	Cytochrome P450 2D6 Gene symbol: CYP2D6 UniProt: P10635	CYP2D6*38	Not Available	2587_2590delGACT (rs72549351)	Effect Inferred	Poor drug metabolizer, lower dose requirements	Details
Nortriptyline	Cytochrome P450 2D6 Gene symbol: CYP2D6 UniProt: P10635	CYP2D6*36	Not Available	100C>T (rs1065852) -1426C>T variable number of A’s in the region -1258 to -1237a 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*38	Not Available	2587_2590delGACT (rs72549351)	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*36	Not Available	100C>T (rs1065852) -1426C>T variable number of A’s in the region -1258 to -1237a 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*38	Not Available	2587_2590delGACT (rs72549351)	Effect Inferred	Poor response to drug treatment, shorter time to relapse	Details
Desipramine	Cytochrome P450 2D6 Gene symbol: CYP2D6 UniProt: P10635	CYP2D6*36	Not Available	100C>T (rs1065852) -1426C>T variable number of A’s in the region -1258 to -1237a 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*38	Not Available	2587_2590delGACT (rs72549351)	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*36	Not Available	100C>T (rs1065852) -1426C>T variable number of A’s in the region -1258 to -1237a 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*38	Not Available	2587_2590delGACT (rs72549351)	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*36	Not Available	100C>T (rs1065852) -1426C>T variable number of A’s in the region -1258 to -1237a show all 9 …	Effect Inferred	Poor drug metabolizer, increased side effects.	Details
Atomoxetine	Cytochrome P450 2D6 Gene symbol: CYP2D6 UniProt: P10635	CYP2D6*38	Not Available	2587_2590delGACT (rs72549351)	Effect Inferred	Poor drug metabolizer, increased side effects.	Details