Genotyping of <i>CYP2D6</i> Polymorphisms by MALDI-TOF Mass Spectrometry in Sardinian People

Falzoi, Matteo; Pira, Luigi; Lazzari, Paolo; Pani, Luca

doi:10.5402/2013/609797

Cited by 2 publications

(2 citation statements)

References 13 publications

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“…Variants were tested using Agena iPlex chemistry and the MassArray system (Agena Bioscience, San Diego CA, USA), with assays designed using the Agena Cx online tools (currently https://agenacx.com ), and a method similar to that reported by Falzoi et al [ 31 ], with an independent preamplification of CYP2D6 in a long-range PCR. The PCR products were verified on a 1% agarose gel.…”

Section: Methodsmentioning

confidence: 99%

CYP2D6 phenotype, tamoxifen, and risk of contralateral breast cancer in the WECARE Study

et al. 2018

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BackgroundTamoxifen treatment greatly reduces a woman’s risk of developing a second primary breast cancer. There is, however, substantial variability in treatment response, some of which may be attributed to germline genetic variation. CYP2D6 is a key enzyme in the metabolism of tamoxifen to its active metabolites, and variants in this gene have been associated with reduced tamoxifen metabolism. The impact of variation on risk of contralateral breast cancer (CBC) is unknown.MethodsGermline DNA from 1514 CBC cases and 2203 unilateral breast cancer controls was genotyped for seven single nucleotide polymorphisms, one three-nucleotide insertion-deletion, and a full gene deletion. Each variant has an expected impact on enzyme activity, which in combination allows for the classification of women as extensive, intermediate, and poor metabolizers (EM, IM, and PM respectively). Each woman was assigned one of six possible diplotypes and a corresponding CYP2D6 activity score (AS): EM/EM (AS = 2), EM/IM (AS = 1.5), EM/PM (AS = 1), IM/IM (AS = 0.75), IM/PM (AS = 0.5), and PM/PM (AS = 0). We also collapsed categories of the AS to generate an overall phenotype (EM, AS ≥ 1; IM, AS = 0.5–0.75; PM, AS = 0). Rate ratios (RRs) and 95% confidence intervals (CIs) for the association between tamoxifen treatment and risk of CBC in our study population were estimated using conditional logistic regression, stratified by AS.ResultsAmong women with AS ≥ 1 (i.e., EM), tamoxifen treatment was associated with a 20–55% reduced RR of CBC (AS = 2, RR = – 0.81, 95% CI 0.62–1.06; AS = 1.5, RR = 0.45, 95% CI 0.30–0.68; and AS = 1, RR = 0.55, 95% CI 0.40–0.74). Among women with no EM alleles and at least one PM allele (i.e., IM and PM), tamoxifen did not appear to impact the RR of CBC in this population (AS = 0.5, RR = 1.08, 95% CI 0.59–1.96; and AS = 0, RR = 1.17, 95% CI 0.58–2.35) (p for homogeneity = – 0.02).ConclusionThis study suggests that the CYP2D6 phenotype may contribute to some of the observed variability in the impact of tamoxifen treatment for a first breast cancer on risk of developing CBC.Electronic supplementary materialThe online version of this article (10.1186/s13058-018-1083-y) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

CYP2D6 phenotype, tamoxifen, and risk of contralateral breast cancer in the WECARE Study

et al. 2018

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“…A single study systematically analyzed the allele frequencies of the variants of the CYP2D6 gene in a sample comprised of 250 healthy volunteers of Sardinian origin (Falzoi et al ., 2013). Some of these variants showed a different frequency in the Sardinian population than that reported for most other European populations (Falzoi et al ., 2013; Mizzi et al ., 2016). Conversely, to our knowledge, no study analyzed differences in frequencies of CYP2C19 phenotypes between Sardinians and other populations.…”

Section: Introductionmentioning

confidence: 99%

Protocol for a pharmacogenetic study of antidepressants: characterization of drug-metabolizing profiles of cytochromes CYP2D6 and CYP2C19 in a Sardinian population of patients with major depressive disorder

Pinna

Manchia

Pisanu

et al. 2021

Psychiatric Genetics

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The effectiveness of antidepressants shows high interindividual variability ranging from full symptomatologic remission to treatment-resistant depression. Many factors can determine the variation in the clinical response, but a fundamental role is played by genetic variation within the genes encoding for the enzymes most involved in the metabolism of antidepressant drugs: the CYP2D6 and CYP2C19 isoforms of the cytochrome P450 system. This study is poised to clarify whether the different metabolizing phenotypes related to CYP2D6 and CYP2C19 could have an impact on the clinical efficacy of antidepressants and whether the frequency of these phenotypes of metabolization shows differences in the population of Sardinian patients compared to other Caucasian populations. The sample is being recruited from patients followed-up and treated at the Psychiatric Unit of the

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Genotyping of CYP2D6 Polymorphisms by MALDI-TOF Mass Spectrometry in Sardinian People

Cited by 2 publications

References 13 publications

CYP2D6 phenotype, tamoxifen, and risk of contralateral breast cancer in the WECARE Study

CYP2D6 phenotype, tamoxifen, and risk of contralateral breast cancer in the WECARE Study

Protocol for a pharmacogenetic study of antidepressants: characterization of drug-metabolizing profiles of cytochromes CYP2D6 and CYP2C19 in a Sardinian population of patients with major depressive disorder

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