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Author (up) Baber, M.; Chaudhry, S.; Kelly, L.; Ross, C.; Carleton, B.; Berger, H.; Koren, G. file  url
openurl 
  Title The pharmacogenetics of codeine pain relief in the postpartum period Type Journal Article
  Year 2015 Publication The Pharmacogenomics Journal Abbreviated Journal Pharmacogenomics J  
  Volume 15 Issue 5 Pages 430-435  
  Keywords Adult; Cesarean Section/adverse effects; Codeine/*administration & dosage; Female; Genotype; Glucuronosyltransferase/*genetics; Humans; Pain/drug therapy/*genetics/pathology; Pain Management; Pharmacogenetics; Polymorphism, Single Nucleotide; Postpartum Period; Pregnancy; Receptors, Opioid, mu/*genetics  
  Abstract The objective of this study was to examine interindividual variability in codeine requirements and pain management by examining select genetic polymorphisms in the codeine pharmacological pathway. The study included a nested cohort of 98 women who were prescribed codeine following cesarean section. Participants were genotyped for select polymorphisms of the COMT, ABCB1, CYP2D6, UGT2B7 and OPRM1 genes and instructed to describe their level of pain using the visual analog scale (mm) 1 h following each dose of codeine. Analysis revealed that reported pain increases with maternal age (P=0.041). Asians required more codeine than Caucasians (P=0.048). Significant differences in mean dose consumption were seen among the genotypic groups of the OPRM1 A118G (P=0.001) and UGT2B7 C802T (P=0.015) variants. These variants were found to predict codeine consumption in the cohort overall (P=0.000) and among Caucasians (P=0.001). These findings will assist in customizing therapy to effectively manage postpartum pain.  
  Call Number Serial 1573  
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Author (up) Parsons, A.B.; Brost, R.L.; Ding, H.; Li, Z.; Zhang, C.; Sheikh, B.; Brown, G.W.; Kane, P.M.; Hughes, T.R.; Boone, C. file  url
doi  openurl
  Title Integration of chemical-genetic and genetic interaction data links bioactive compounds to cellular target pathways Type Journal Article
  Year 2004 Publication Nature Biotechnology Abbreviated Journal Nat Biotechnol  
  Volume 22 Issue 1 Pages 62-69  
  Keywords Biotechnology/*methods; Cluster Analysis; Drug Industry/*methods; *Drug Resistance; Fungal Proteins/metabolism; Gene Deletion; *Gene Expression Regulation; Mutation; Pharmacogenetics; Proton-Translocating ATPases/metabolism; Saccharomyces cerevisiae/*genetics; Software  
  Abstract Bioactive compounds can be valuable research tools and drug leads, but it is often difficult to identify their mechanism of action or cellular target. Here we investigate the potential for integration of chemical-genetic and genetic interaction data to reveal information about the pathways and targets of inhibitory compounds. Taking advantage of the existing complete set of yeast haploid deletion mutants, we generated drug-hypersensitivity (chemical-genetic) profiles for 12 compounds. In addition to a set of compound-specific interactions, the chemical-genetic profiles identified a large group of genes required for multidrug resistance. In particular, yeast mutants lacking a functional vacuolar H(+)-ATPase show multidrug sensitivity, a phenomenon that may be conserved in mammalian cells. By filtering chemical-genetic profiles for the multidrug-resistant genes and then clustering the compound-specific profiles with a compendium of large-scale genetic interaction profiles, we were able to identify target pathways or proteins. This method thus provides a powerful means for inferring mechanism of action.  
  Call Number Serial 339  
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Author (up) Zai, G.; Brandl, E.J.; Muller, D.J.; Richter, M.A.; Kennedy, J.L. file  url
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  Title Pharmacogenetics of antidepressant treatment in obsessive-compulsive disorder: an update and implications for clinicians Type Journal Article
  Year 2014 Publication Pharmacogenomics Abbreviated Journal Pharmacogenomics  
  Volume 15 Issue 8 Pages 1147-1157  
  Keywords Antidepressive Agents/adverse effects/*therapeutic use; Cytochrome P-450 Enzyme System/genetics; Humans; Inactivation, Metabolic; Obsessive-Compulsive Disorder/*drug therapy/genetics/pathology; *Pharmacogenetics; Serotonin Uptake Inhibitors/adverse effects/*therapeutic use; Ocd; antidepressant/drug/treatment response; cytochrome P450 drug metabolism/system; genetics; obsessive-compulsive and related disorders; obsessive-compulsive disorder; pharmacogenetics  
  Abstract Obsessive-compulsive disorder (OCD) is a chronic neuropsychiatric disorder with high genetic influence. Antidepressants such as serotonin reuptake inhibitors, are widely accepted as the first-line medications for OCD; however, approximately 50% of OCD patients show poor response. Personalized medicine utilizing genetic testing has recently received much attention because the variability of antidepressant response and tolerability are partly due to an individual's genetic variations. This has led to researchers investigating the role of specific genetic factors on antidepressant response and utility of testing in the clinical realm. Genetic test panels are showing promise for guiding antidepressant treatment to improve outcomes in depression. This article will review the most recent findings in the pharmacogenetics of OCD and its related disorders. Promising results have been reported for several serotonergic and glutamatergic system genes and the cytochrome CYP450 liver enzyme genes, which appear to play an important role in OCD and antidepressant response.  
  Call Number Serial 1766  
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