Cytochrome P4502D6 (CYP2D6) gene locus heterogeneity: characterization of gene duplication events.

Cytochrome P4502D6 (CYP2D6) gene locus heterogeneity: characterization of gene duplication events. Research Abstract Details 

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Cytochrome P4502D6 (CYP2D6) gene locus heterogeneity: characterization of gene duplication events. Abstract Text:

A Gaedigk,L ,K Divakaran,L Dianne Bradford,I Zineh,T F Oberlander,D C Brousseau,D G McCarver,J A Johnson,S W Alander,K Wayne Riggs,J Steven Leeder,

Duplications and multiplications of active CYP2D6 genes can cause ultrarapid drug metabolism and lead to therapeutic failure. Multiple functional and non-functional duplication alleles have been further characterized. Duplications were detected by long-range polymerase chain reaction (PCR), PCR-restriction fragment length polymorphism, and sequence analysis. A PCR fragment encompassing the entire duplicated gene was utilized for detailed characterization. Duplications occurred at 1.3, 5.75, and 2.0% in Caucasian, African American, and racially mixed populations, respectively (n=887 total). Of those 28, 47, and 17% were non-functional CYP2D6*4 x N. Twelve unique duplication alleles were detected: *1 x N, *2 x N, *4 x N, *6 x N, *10 x N, *17 x N, *17 x N[spacer], *29 x N, *35 x N, *43 x N, *45 x N, and a novel non-functional tandem arrangement of a chimeric 2D7/2D6 and *1 gene. All novel duplications except *35 x N were found in African Americans. Accurate identification of gene duplication events is essential to avoid false-positive ultrarapid metabolism assignments and thus, overestimation of predicted activity and increased risk for unwanted adverse events.

Cytochrome P4502D6 (CYP2D6) gene locus heterogeneity: characterization of gene duplication events. Publishing Authors By Initials

A Gaedigk,L ,K Divakaran,L Dianne Bradford,I Zineh,TF Oberlander,DC Brousseau,DG McCarver,JA Johnson,SW Alander,K Wayne Riggs,J Steven Leeder,

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Cytochrome P4502D6 (CYP2D6) gene locus heterogeneity: characterization of gene duplication events. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Clinical pharmacology and therapeutics

VOLUME: 81

Page Numbers: 242-51

Journal Abbreviation: Clin. Pharmacol. Ther.

ISSN: 0009-9236

DAY: 3

MONTH: Feb

YEAR: 2007

Cytochrome P4502D6 (CYP2D6) gene locus heterogeneity: characterization of gene duplication events. Information

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LANGUAGE: eng

NlmUniqueID: 372741

Cytochrome P4502D6 (CYP2D6) gene locus heterogeneity: characterization of gene duplication events. Keywords Mesh Terms:

KEYWORDS: Predictive Value of Tests

MESH TERMS: genetics

Chemical & Substance for Abstract: Cytochrome P4502D6 (CYP2D6) gene locus heterogeneity: characterization of gene duplication events. Information

Substance Name: Cytochrome P-450 CYP2D6

Registry Number: EC 1.14.14.1

Grant and Affiliation Information for Cytochrome P4502D6 (CYP2D6) gene locus heterogeneity: characterization of gene duplication events.

AFFILIATION: Section of Developmental Pharmacology & Experimental Therapeutics, The Children's Mercy Hospital and Clinics, Kansas City, Missouri, USA. agaedigk@cmh.edu

Country: United States

AGENCY: United States NCRR

GRANT: M01-RR00082

ACRONYM: RR

MEDLINETA: Clin Pharmacol Ther

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