Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for Codeine Therapy in the Context of Cytochrome P450 2D6 (CYP2D6) Genotype

Crews, Kristine R.; Gaedigk, Andrea; Dunnenberger, Henry M.; Klein, Teri E.; Shen, Danny D.; Callaghan, John T.; Kharasch, Evan D.; Skaar, Todd C.

doi:10.1038/clpt.2011.287

Cited by 330 publications

(279 citation statements)

References 40 publications

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“…CYP2D6*10 is reported to be present in 11-70% of Asian populations [41,60], while it is seldom higher than 10% in populations of African origin [8,59]. CYP2D6*17 and CYP2D6*29, among others, are accepted as being African-specific alleles, and are present at frequencies of up to 34% and 29%, respectively .…”

Section: Cyp2c19 Cyp2d6 and The Management Of Major Depressive Disormentioning

confidence: 99%

“…are seldom observed [59]. CYP2D6*5 is characterized by a deletion of the entire gene, and is present at similar frequencies of less than 10% in all populations, with the exception of a handful of African populations, where the allele may be as frequent as 19% [8].…”

Section: Cyp2c19 Cyp2d6 and The Management Of Major Depressive Disormentioning

confidence: 99%

“…CYP2D6*17 and CYP2D6*29, among others, are accepted as being African-specific alleles, and are present at frequencies of up to 34% and 29%, respectively . In contrast, these alleles are either absent or occur at frequencies of less than 1% in Asian and Caucasian populations [59]. The reduced function allele CYP2D6*41 has also been investigated in Africa, and, on average, is harbored by 10% of African individuals [8,59].…”

Section: Cyp2c19 Cyp2d6 and The Management Of Major Depressive Disormentioning

confidence: 99%

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Priority pharmacogenetics for the African continent: focus on CYP450

Alessandrini

Pepper

2014

Pharmacogenomics

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SummaryCountries in Africa have a high burden of communicable disease, and are experiencing an increase in non-communicable diseases due to the effects of globalization, industrialization and urbanization.The costs incurred through adverse drug reactions and non-responsiveness to therapy further aggravate the situation, and the application of pharmacogenetic principles is likely to provide some relief. Having undertaken an extensive evaluation of CYP450 reports in Africa, our objective was to map out areas of need based on regional disease burdens. The data confirms a paucity of CYP450 reports and illustrates large regions for which no population information exists. There is a dire need to address the health problems of Africa, and wide-scale pharmacogenetic profiling of these populations will add significantly to improving patient care on the continent. Priority pharmacogenetics for the African continent gives precedence to the profiling of clinically relevant pharmacogenetic biomarkers, and defines the immediate need in the context of disease burden.

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Section: Cyp2c19 Cyp2d6 and The Management Of Major Depressive Disormentioning

confidence: 99%

Section: Cyp2c19 Cyp2d6 and The Management Of Major Depressive Disormentioning

confidence: 99%

Section: Cyp2c19 Cyp2d6 and The Management Of Major Depressive Disormentioning

confidence: 99%

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Priority pharmacogenetics for the African continent: focus on CYP450

Alessandrini

Pepper

2014

Pharmacogenomics

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“…Clinically significant toxic effects related to opioid excess have been reported in ultrarapid metabolizers, which suggests that the risk of toxic effects from codeine depends, in part, on genotype. 1 In April 2012, a case series was published reporting two deaths and one case of respiratory depression in children 3 to 5 years of age who had received typical doses of codeine after tonsillectomy, adenoidectomy, or both performed because of obstructive sleep apnea. 2 The two deaths occurred in children who had evidence of being ultrarapid metabolizers, and the postmortem morphine levels in these children were substantially high- er than the therapeutic range.…”

mentioning

confidence: 99%

“…1 The gene encoding CYP2D6 has many genetic variations that affect the amount of codeine that is converted to an active form and that result in the drug's variable effect. Patients with a normal range of CYP2D6 activity represent 75 to 92% of the population and are called extensive metabolizers.…”

mentioning

confidence: 99%

New Evidence about an Old Drug — Risk with Codeine after Adenotonsillectomy

Racoosin¹,

Roberson²,

Pacanowski³

et al. 2013

N Engl J Med

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Clinical Interpretation and Implications of Whole-Genome Sequencing

Dewey

Grove

Pan

et al. 2014

JAMA

408

386

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IMPORTANCE Whole-genome sequencing (WGS) is increasingly applied in clinical medicine and is expected to uncover clinically significant findings regardless of sequencing indication. OBJECTIVES To examine coverage and concordance of clinically relevant genetic variation provided by WGS technologies; to quantitate inherited disease risk and pharmacogenomic findings in WGS data and resources required for their discovery and interpretation; and to evaluate clinical action prompted by WGS findings. DESIGN, SETTING, AND PARTICIPANTS An exploratory study of 12 adult participants recruited at Stanford University Medical Center who underwent WGS between November 2011 and March 2012. A multidisciplinary team reviewed all potentially reportable genetic findings. Five physicians proposed initial clinical follow-up based on the genetic findings. MAIN OUTCOMES AND MEASURES Genome coverage and sequencing platform concordance in different categories of genetic disease risk, person-hours spent curating candidate disease-risk variants, interpretation agreement between trained curators and disease genetics databases, burden of inherited disease risk and pharmacogenomic findings, and burden and interrater agreement of proposed clinical follow-up. RESULTS Depending on sequencing platform, 10% to 19% of inherited disease genes were not covered to accepted standards for single nucleotide variant discovery. Genotype concordance was high for previously described single nucleotide genetic variants (99%-100%) but low for small insertion/deletion variants (53%-59%). Curation of 90 to 127 genetic variants in each participant required a median of 54 minutes (range, 5-223 minutes) per genetic variant, resulted in moderate classification agreement between professionals (Gross κ, 0.52; 95%CI, 0.40-0.64), and reclassified 69%of genetic variants cataloged as disease causing in mutation databases to variants of uncertain or lesser significance. Two to 6 personal disease-risk findings were discovered in each participant, including 1 frameshift deletion in the BRCA1 gene implicated in hereditary breast and ovarian cancer. Physician review of sequencing findings prompted consideration of a median of 1 to 3 initial diagnostic tests and referrals per participant, with fair interrater agreement about the suitability of WGS findings for clinical follow-up (Fleiss κ, 0.24; P < 001). CONCLUSIONS AND RELEVANCE In this exploratory study of 12 volunteer adults, the use of WGS was associated with incomplete coverage of inherited disease genes, low reproducibility of detection of genetic variation with the highest potential clinical effects, and uncertainty about clinically reportable findings. In certain cases, WGS will identify clinically actionable genetic variants warranting early medical intervention. These issues should be considered when determining the role of WGS in clinical medicine.

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Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for Codeine Therapy in the Context of Cytochrome P450 2D6 (CYP2D6) Genotype

Cited by 330 publications

References 40 publications

Priority pharmacogenetics for the African continent: focus on CYP450

Priority pharmacogenetics for the African continent: focus on CYP450

New Evidence about an Old Drug — Risk with Codeine after Adenotonsillectomy

Clinical Interpretation and Implications of Whole-Genome Sequencing

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