Novel CYP2D6 and CYP2C19 variants identified in a patient with adverse reactions towards venlafaxine monotherapy and dual therapy with nortriptyline and fluoxetine

Eng Wee Chua, James Foulds, Allison L. Miller, Martin A. Kennedy

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

We present a case report of novel variants of CYP2D6 and CYP2C19 identified in a patient who experienced adverse effects during antidepressant therapy. CYP2D6 DNA sequencing revealed that the patient was most likely an intermediate metabolizer, owing to the presence of a novel variant (2579C>T), which gives rise to a premature stop codon in exon 5. Because defects in CYP2C19 may also be important, we sequenced the promoter region and all exons of CYP2C19 and identified a cluster of three novel variants (-13G>A, 7C>T and 10T>C) around exon 1, as well as the more common CYP2C19*2 allele. The presence of multiple genetic lesions in CYP2C19 implies that this patient is potentially a CYP2C19 poor metabolizer, and this was confirmed by haplotype analysis. Combined impairment of CYP2D6 and CYP2C19 activities, we believe, may have contributed to the development of the observed drug responses in the present report.

Original languageEnglish
Pages (from-to)494-497
Number of pages4
JournalPharmacogenetics and Genomics
Volume23
Issue number9
DOIs
Publication statusPublished - Sep 2013

Fingerprint

Nortriptyline
Cytochrome P-450 CYP2D6
Fluoxetine
Exons
Therapeutics
Nonsense Codon
Cytochrome P-450 CYP2C19
Venlafaxine Hydrochloride
DNA Sequence Analysis
Genetic Promoter Regions
Haplotypes
Antidepressive Agents
Alleles

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Molecular Medicine
  • Genetics(clinical)

Cite this

Novel CYP2D6 and CYP2C19 variants identified in a patient with adverse reactions towards venlafaxine monotherapy and dual therapy with nortriptyline and fluoxetine. / Chua, Eng Wee; Foulds, James; Miller, Allison L.; Kennedy, Martin A.

In: Pharmacogenetics and Genomics, Vol. 23, No. 9, 09.2013, p. 494-497.

Research output: Contribution to journalArticle

@article{2b58139a986042ba84f2e95f3a5b8401,
title = "Novel CYP2D6 and CYP2C19 variants identified in a patient with adverse reactions towards venlafaxine monotherapy and dual therapy with nortriptyline and fluoxetine",
abstract = "We present a case report of novel variants of CYP2D6 and CYP2C19 identified in a patient who experienced adverse effects during antidepressant therapy. CYP2D6 DNA sequencing revealed that the patient was most likely an intermediate metabolizer, owing to the presence of a novel variant (2579C>T), which gives rise to a premature stop codon in exon 5. Because defects in CYP2C19 may also be important, we sequenced the promoter region and all exons of CYP2C19 and identified a cluster of three novel variants (-13G>A, 7C>T and 10T>C) around exon 1, as well as the more common CYP2C19*2 allele. The presence of multiple genetic lesions in CYP2C19 implies that this patient is potentially a CYP2C19 poor metabolizer, and this was confirmed by haplotype analysis. Combined impairment of CYP2D6 and CYP2C19 activities, we believe, may have contributed to the development of the observed drug responses in the present report.",
author = "Chua, {Eng Wee} and James Foulds and Miller, {Allison L.} and Kennedy, {Martin A.}",
year = "2013",
month = "9",
doi = "10.1097/FPC.0b013e328363688d",
language = "English",
volume = "23",
pages = "494--497",
journal = "Pharmacogenetics and Genomics",
issn = "1744-6872",
publisher = "Lippincott Williams and Wilkins",
number = "9",

}

TY - JOUR

T1 - Novel CYP2D6 and CYP2C19 variants identified in a patient with adverse reactions towards venlafaxine monotherapy and dual therapy with nortriptyline and fluoxetine

AU - Chua, Eng Wee

AU - Foulds, James

AU - Miller, Allison L.

AU - Kennedy, Martin A.

PY - 2013/9

Y1 - 2013/9

N2 - We present a case report of novel variants of CYP2D6 and CYP2C19 identified in a patient who experienced adverse effects during antidepressant therapy. CYP2D6 DNA sequencing revealed that the patient was most likely an intermediate metabolizer, owing to the presence of a novel variant (2579C>T), which gives rise to a premature stop codon in exon 5. Because defects in CYP2C19 may also be important, we sequenced the promoter region and all exons of CYP2C19 and identified a cluster of three novel variants (-13G>A, 7C>T and 10T>C) around exon 1, as well as the more common CYP2C19*2 allele. The presence of multiple genetic lesions in CYP2C19 implies that this patient is potentially a CYP2C19 poor metabolizer, and this was confirmed by haplotype analysis. Combined impairment of CYP2D6 and CYP2C19 activities, we believe, may have contributed to the development of the observed drug responses in the present report.

AB - We present a case report of novel variants of CYP2D6 and CYP2C19 identified in a patient who experienced adverse effects during antidepressant therapy. CYP2D6 DNA sequencing revealed that the patient was most likely an intermediate metabolizer, owing to the presence of a novel variant (2579C>T), which gives rise to a premature stop codon in exon 5. Because defects in CYP2C19 may also be important, we sequenced the promoter region and all exons of CYP2C19 and identified a cluster of three novel variants (-13G>A, 7C>T and 10T>C) around exon 1, as well as the more common CYP2C19*2 allele. The presence of multiple genetic lesions in CYP2C19 implies that this patient is potentially a CYP2C19 poor metabolizer, and this was confirmed by haplotype analysis. Combined impairment of CYP2D6 and CYP2C19 activities, we believe, may have contributed to the development of the observed drug responses in the present report.

UR - http://www.scopus.com/inward/record.url?scp=84882252507&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84882252507&partnerID=8YFLogxK

U2 - 10.1097/FPC.0b013e328363688d

DO - 10.1097/FPC.0b013e328363688d

M3 - Article

C2 - 23799451

AN - SCOPUS:84882252507

VL - 23

SP - 494

EP - 497

JO - Pharmacogenetics and Genomics

JF - Pharmacogenetics and Genomics

SN - 1744-6872

IS - 9

ER -