An efficient strategy for detection of known and new mutations of the CYP2D6 gene using single strand conformation polymorphism analysis

Broly, F.; Marez, Delphine; Sabbagh, N; Legrand, M.; Millecamps, Stéphanie; Lo-Guidice, Jean-Marc; Boone, Philip M.; Meyer, Urs

doi:10.1097/00008571-199512000-00006

Cited by 67 publications

(25 citation statements)

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“…The CYP2D6 genotype was determined before the beginning of the treatment, using single-strand conformation polymorphism analysis (SSCP) of the gene amplified by polymerase chain reaction (PCR) analysis by Broly et al (1995).…”

Section: Cyp2d6 Genotype Determinationmentioning

confidence: 99%

Clomipramine, fluoxetine and CYP2D6 metabolic capacity in depressed patients

Vandel

Haffen

Nezelof

et al. 2004

Human Psychopharmacology

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Cytochrome P450-2D6 may be involved in the metabolism of many drugs such as psychotropic drugs and its genetic polymorphism is responsible for inter-individual differences in the therapeutic effect and toxicity of these drugs. Moreover with the same genetic basis, CYP2D6 metabolic capacity variations are observed. Different factors of variation may be involved, among them the prescribed drugs. The aim of this study was to compare the influence of two types of antidepressants, tricyclic (clomipramine) and serotonergic specific recapture inhibitor (SSRI) (fluoxetine), on the CYP2D6 metabolic capacity of depressed inpatients. The CYP2D6 phenotype (dextromethorphan test) was determined in 56 genotyped (PCR-SSCP) depressed caucasian inpatients with a heterozygous genotype. Forty-five subjects were treated with clomipramine and eleven received fluoxetine. The dextromethorphan metabolic ratio (MR) median was significantly higher in the fluoxetine group (0.255) than in the clomipramine group (0.083, p < 0.014). In this study, fluoxetine involved a greater decrease of CYP2D6 metabolic capacity than clomipramine. Clinical implications and the possible connection between a decreased CYP2D6 activity and adverse drug effects were discussed. Caution should be taken when drugs with a low therapeutic index must be coprescribed in such patients.

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Section: Cyp2d6 Genotype Determinationmentioning

confidence: 99%

Clomipramine, fluoxetine and CYP2D6 metabolic capacity in depressed patients

Vandel

Haffen

Nezelof

et al. 2004

Human Psychopharmacology

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“…PCR-single-strand conformational polymorphism (SSCP) analysis was used to determine the frequencies of mutant alleles G1601A (exon 13, Ser534Asn) and A1627G (exon 13, Ile543Val) (Broly et al, 1995). A 255-bp PCR fragment corresponding to the mutated region of exon 13 was amplified from human genomic DNA using a forward primer DPD70F (Table 2) and a reverse primer 5Ј-AGCTCTTC-GAATCATTGATG-3Ј.…”

Section: Genotyping Of the Mutant Alleles By Pcr-rflp And Sscpmentioning

confidence: 99%

Characterization of the Human Dihydropyrimidine Dehydrogenase Gene

et al. 1998

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“…30,31 Additional allelic variants have been more recently described but their effect on metabolic activity remains to be determined. 27 To investigate the nine exons of the CYP2D6 gene as well as its locus, we analyzed DNA from 109 patients with sporadic PD and 514 control subjects using the previously combined methods based on the single-strand conformation polymorphism analysis of DNA fragments amplified by polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) 32 and restriction fragment length polymorphism (RFLP) assay. 33,34 We also fully characterized CYP2D6 alleles in DNAs from 68 members of families with PD patients, having 18 affected members and 50 unaffected relatives, by the same methods.…”

Section: Discussionmentioning

confidence: 99%