Genomics|Update|Current - Genomics in the Scientific Literature - Pharmacogenomics

Genomics in the Scientific Literature
Topics in the Scientific Literature

Pharmacogenomics
1. Cost-effectiveness analysis in pharmacogenomics
Payne K & Shabaruddin FH
Pharmacogenomics 2010 May;11(5):643-6

Pharmacogenomics. 2010 May;11(5):643-6.

Cost-effectiveness analysis in pharmacogenomics.
Payne K, Shabaruddin FH.

Health Sciences-Economics, School of Community Based Medicine, The University of Manchester, Manchester, UK. Katherine.payne@manchester.ac.uk

Abstract
The existence of finite healthcare budgets drives the need to consider opportunity cost and demonstrate that pharmacogenomic interventions offer added value, in terms of the relative costs and benefits, compared with current practice. This is where the framework of cost-effectiveness analysis is useful. Existing systematic reviews of economic evaluations of genetic technologies have all highlighted the need to improve the quality of the economics evidence base. More recent cost-effectiveness analyses of pharmacogenomics are generally of higher quality. The future will see an increase in the number of published cost-effectiveness analyses. Critical appraisal of these analyses is necessary to ensure the evidence base is sufficiently robust to inform resource allocation decisions at local and national levels.

PMID: 20415553 [PubMed - in process]Free Article
http://www.ncbi.nlm.nih.gov/pubmed/20415553?dopt=Abstract



2. Direct-to-consumer genome testing: opportunities for pharmacogenomics research?
Prainsack B & Wolinsky H
Pharmacogenomics 2010 May;11(5):651-5

Pharmacogenomics. 2010 May;11(5):651-5.

Direct-to-consumer genome testing: opportunities for pharmacogenomics research?
Prainsack B, Wolinsky H.

King's College London, Centre for Biomedicine & Society (CBAS), London, UK. barbara.prainsack@kcl.ac.uk

Abstract
This commentary examines the role that commercial providers of SNP-based genome-wide personalized risk profiles play in facilitating pharmacogenomics research. We first take a look at how personal genomics services, exemplified by the company 23andMe, communicate information on drug response to customers. We then discuss the most important benefits and issues we see arising with the idea of 'crowdsourcing' pharmacogenomics research via commercial genome-scan providers. We conclude with a brief vision for the future.

PMID: 20415555 [PubMed - in process]Free Article
http://www.ncbi.nlm.nih.gov/pubmed/20415555?dopt=Abstract



3. How and Why to Screen for CYP2D6 Interindividual Variability in Patients Under Pharmacological Treatments
De Gregori M, et al.
Curr Drug Metab 2010 Mar;11(3):276-82

Curr Drug Metab. 2010 Mar 1;11(3):276-82.

How and Why to Screen for CYP2D6 Interindividual Variability in Patients Under Pharmacological Treatments.
De Gregori M, Allegri M, De Gregori S, Garbin G, Tinelli C, Regazzi M, Govoni S, Ranzani GN.

Department of Genetics and Microbiology, University of Pavia, Italy. ranzani@ipvgen.unipv.it.

Abstract
Cytochromes P450 are members of a superfamily of hemoproteins that catalyze a variety of oxidative reactions in the metabolism of endogenous and exogenous hydrophobic substrates. Fifty-eight cytochrome P450 (CYP) isoenzymes belonging to 18 families have been identified in human cells; the corresponding genes are highly polymorphic, and genetic variability underlies interindividual differences in drug response. The polymorphisms of CYP2D6 significantly affect the pharmacokinetics of about 50% of the drugs in clinical use, which are CYP2D6 substrates. The number of functional CYP2D6 alleles per genome determines the existence of four different phenotypes, i.e. poor, intermediate, extensive, and ultrarapid metabolizers. CYP2D6 genetic variants include copy number variations, single nucleotide substitutions, frameshift and insertion/deletion mutations. This review reports some of the different methodological approaches used to screen for CYP2D6 variants and focuses on methods that have improved variation detection, from conventional techniques to more recent microarray technology and high throughput DNA sequencing. In addition, this review reports some results on clinical relevance of CYP2D6 polymorphisms and provides examples of variability in drug response associated with interindividual phenotypic differences.

PMID: 20408805 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/pubmed/20408805?dopt=Abstract



4. Pharmacogenomics--10 years of progress: a cardiovascular perspective
Winkelmann BR & Herrington D
Pharmacogenomics 2010 May;11(5):613-6

Pharmacogenomics. 2010 May;11(5):613-6.

Pharmacogenomics--10 years of progress: a cardiovascular perspective.
Winkelmann BR, Herrington D.

Johann Wolfgang Goethe University, Frankfurt, ClinPhenomics GmbH & Kardiologie Frankfurt-Sachsenhausen, Frankfurt, Germany. winkbr@gmx.de

Abstract
In 2000, the year the first issue of Pharmacogenomics was launched, completion of the human genome sequence was publicly applauded, although in reality it took a few more years to obtain the first full sequence data. Within 10 years, sequencing technology has advanced to an extent seemed unreachable at that time. Whilst, in 2000, it took many years to sequence just one human genome, today such sequencing can be done within 1-2 weeks. Human genetic variation has been catalogued in depth to at least 5% prevalence in Caucasians and efforts are underway to broaden this coverage to at least 1%. Haplotype maps have been constructed to extract the most informative SNPs for genetic studies. Genome-wide association studies based on 500,000 to 1 million such SNPs for mapping and gene detection efforts are the norm today. Genotype-guided therapy is emerging into mainstream medicine, setting the stage for a future of personalized medicine as compared to today's group-based medicine, where therapeutic efficacy is defined from mean effects in large-scale Phase III studies in humans.

PMID: 20415546 [PubMed - in process]Free Article
http://www.ncbi.nlm.nih.gov/pubmed/20415546?dopt=Abstract



5. Real-world clinical effectiveness, regulatory transparency and payer coverage: three ingredients for translating pharmacogenomics into clinical practice
Frueh FW
Pharmacogenomics 2010 May;11(5):657-60

Pharmacogenomics. 2010 May;11(5):657-60.

Real-world clinical effectiveness, regulatory transparency and payer coverage: three ingredients for translating pharmacogenomics into clinical practice.
Frueh FW.

R&D Personalized Medicine, Medco Health Solutions, Inc., Bethesda, MD 20814, USA. felix_frueh@medco.com

Abstract
The past decade of pharmacogenomics was driven by the sequencing of the human genome to create ever denser maps of genetic variations for studying the diversity across individuals. Today, genotyping technology is available at a fraction of the cost of what it was 10 years ago and many pharmacogenomic variations have been studied in detail. Still, we are only starting to gain an understanding of how pharmacogenomic-guided drug therapy affects clinical outcomes: real-world studies that demonstrate the clinical effectiveness and address the economic implications of pharmacogenomics are needed to help decide when and how to implement pharmacogenomics in clinical practice, how to regulate pharmacogenomic testing and how the healthcare system will integrate this new science into an environment of rapidly increasing cost.

PMID: 20415556 [PubMed - in process]Free Article
http://www.ncbi.nlm.nih.gov/pubmed/20415556?dopt=Abstract



6. The past, present and future of pharmacoepigenomics
Ingelman-Sundberg M & Gomez A
Pharmacogenomics 2010 May;11(5):625-7

Pharmacogenomics. 2010 May;11(5):625-7.

The past, present and future of pharmacoepigenomics.
Ingelman-Sundberg M, Gomez A.

Department of Physiology & Pharmacology, Karolinska Institutet, Stockholm, Sweden. magnus.ingelman-sundberg@ki.se

Abstract
A significant number of instances of interindividual variability in drug response, where a clear phenotypic consequence is evident in the population, have not yet been associated with variations in gene sequence. Epigenetics, along with, for example, drug interactions and disease, provides answers to some of these inconsistencies. The role of epigenetics in drug response has just started to be perceived, but its impending influence on drug metabolism and disposition promises to be important. Research in this area can provide us with novel mechanisms for this variation and also with novel biomarkers that can be useful for understanding drug response, as well as for the development of new drugs and which can, in addition, constitute predictive biomarkers for today's and tomorrow's pharmacotherapy, yielding a substantial improvement in human health.

PMID: 20415549 [PubMed - in process]Free Article
http://www.ncbi.nlm.nih.gov/pubmed/20415549?dopt=Abstract