Journal ArticleDOI
Pharmacogenomics: Translating Functional Genomics into Rational Therapeutics
William E. Evans,Mary V. Relling +1 more
TLDR
Pharmacogenomic studies are rapidly elucidating the inherited nature of these differences in drug disposition and effects, thereby enhancing drug discovery and providing a stronger scientific basis for optimizing drug therapy on the basis of each patient's genetic constitution.Abstract:
Genetic polymorphisms in drug-metabolizing enzymes, transporters, receptors, and other drug targets have been linked to interindividual differences in the efficacy and toxicity of many medications. Pharmacogenomic studies are rapidly elucidating the inherited nature of these differences in drug disposition and effects, thereby enhancing drug discovery and providing a stronger scientific basis for optimizing drug therapy on the basis of each patient's genetic constitution.read more
Citations
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Journal ArticleDOI
Influence of Life Stress on Depression: Moderation by a Polymorphism in the 5-HTT Gene
Avshalom Caspi,Karen Sugden,Terrie E. Moffitt,Alan Taylor,Ian W. Craig,Hona Lee Harrington,Joseph L. McClay,Jonathan Mill,Judy Martin,Antony W. Braithwaite,Richie Poulton +10 more
TL;DR: Evidence of a gene-by-environment interaction is provided, in which an individual's response to environmental insults is moderated by his or her genetic makeup.
Journal ArticleDOI
Sequence diversity in CYP3A promoters and characterization of the genetic basis of polymorphic CYP3A5 expression.
Peter M. Kuehl,Jiong Zhang,Yvonne S. Lin,Jatinder K. Lamba,Mahfoud Assem,John D. Schuetz,Paul B. Watkins,Ann K. Daly,Steven A. Wrighton,Stephen D. Hall,Patrick Maurel,Mary V. Relling,Cynthia Brimer,Kazuto Yasuda,Raman Venkataramanan,Stephen C. Strom,Kenneth E. Thummel,Mark S. Boguski,Erin G. Schuetz +18 more
TL;DR: CYP3A5 was more frequently expressed in livers of African Americans than in those of Caucasians, and may be the most important genetic contributor to interindividual and interracial differences in CYP3A-dependent drug clearance and in responses to many medicines.
Journal ArticleDOI
Pharmacogenomics — Drug Disposition, Drug Targets, and Side Effects
TL;DR: The existence of large population differences with small intrapatient variability is consistent with inheritance as a determinant of drug response; it is estimated that genetics can account for 20 to 95 percent of variability in drug disposition and effects.
Journal ArticleDOI
Acetylcholinesterase New roles for an old actor
Hermona Soreq,Shlomo Seidman +1 more
TL;DR: The time is ripe to summarize the evidence on a remarkable diversity of acetylcholinesterase functions, as well as some of the long-suspected 'non-classical' actions of this enzyme, which have more recently driven a profound revolution in research.
Journal ArticleDOI
Accessing genetic variation: genotyping single nucleotide polymorphisms
TL;DR: The hope that single nucleotide polymorphisms will allow genes that underlie complex disease to be identified, together with progress in identifying large sets ofSNPs, are the driving forces behind intense efforts to establish the technology for large-scale analysis of SNPs.
References
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MiRP1 Forms IKr Potassium Channels with HERG and Is Associated with Cardiac Arrhythmia
Geoffrey W. Abbott,Federico Sesti,Igor Splawski,Marianne E. Buck,Michael H. Lehmann,Katherine W Timothy,Mark T. Keating,Steve A.N. Goldstein +7 more
TL;DR: A mechanism for acquired arrhythmia is revealed: genetically based reduction in potassium currents that remains clinically silent until combined with additional stressors.
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Association of polymorphisms in the cytochrome P450 CYP2C9 with warfarin dose requirement and risk of bleeding complications
TL;DR: YP2C9 genotyping may identify a subgroup of patients who have difficulty at induction of warfarin therapy and are potentially at a higher risk of bleeding complications.
Journal ArticleDOI
Polymorphic hydroxylation of debrisoquine in man
TL;DR: Family studies supported the view that alicyclic 4-hydroxylation of debrisoquine is controlled by a single autosomal gene and that a defect in this metabolic step is caused by a recessive allele.
Journal ArticleDOI
Overlapping substrate specificities and tissue distribution of cytochrome P450 3A and P-glycoprotein: implications for drug delivery and activity in cancer chemotherapy.
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Pharmacogenomics — Drug Disposition, Drug Targets, and Side Effects
Sequence diversity in CYP3A promoters and characterization of the genetic basis of polymorphic CYP3A5 expression.
Peter M. Kuehl,Jiong Zhang,Yvonne S. Lin,Jatinder K. Lamba,Mahfoud Assem,John D. Schuetz,Paul B. Watkins,Ann K. Daly,Steven A. Wrighton,Stephen D. Hall,Patrick Maurel,Mary V. Relling,Cynthia Brimer,Kazuto Yasuda,Raman Venkataramanan,Stephen C. Strom,Kenneth E. Thummel,Mark S. Boguski,Erin G. Schuetz +18 more