http://adaptivepharmacogenomics.com/ 2011-02-17T03:23:04Z Adaptive Pharmacogenomics, LLC esau.issaks@adaptivepharmacogenomics.com 2011-02-17T03:23:04Z PubMed:20860469

<p><b>Pharmacogenomic implications of variants of monoaminergic-related genes in geriatric psychiatry.</b></p> <p>Pharmacogenomics. 2010 Sep;11(9):1305-30</p> <p>Authors: Shiroma PR, Geda YE, Mrazek DA</p> <p>Response to psychiatric medications in later life is highly heterogeneous and complex. Monoaminergic-related polymorphisms may influence medication response and susceptibility to side effects in elderly individuals. Individuals with the lower function short (S) allele of the serotonin transporter gene (SLC6A4) insertion/deletion (indel) promoter polymorphism (5-HTTLPR) have both increased the likelihood of adverse drug events and increased the need for higher antidepressant concentrations to obtain maximum antidepressant response. By contrast, carriers of the higher expression homozygous long allele (L/L) genotype may respond at lower concentrations. The differential role of these polymorphisms appears at early stages of treatment rather than in the final antidepressant outcome. Research findings suggest that the rs25531 SNP may influence functional expression of the L allele. Similarly, a variable number of tandem repeats in the second intron of the serotonin transporter gene may influence the expression of SLC6A4 and the implications of these variants may be influenced by aging. Two polymorphisms, rs2242466 (-182T/C) and rs5569 (1287G/A), in the norepinephrine transporter gene (SLC6A2 or NET) have been associated with antidepressant response. Studies in dopamine-related polymorphisms have focused on associations with neuroleptic-induced movement disorders. The rs1800497 variant (Taq1A) of the dopamine receptor D2 (DRD2) gene located in a noncoding 3´ region may regulate expression of D2 receptors. The rs6280 variant (Ser9Gly) of the dopamine receptor 3 (DRD3) gene may influence the binding affinity of D3 receptors as a result of serine to glycine substitution of the receptor protein. A multicenter collaborative research effort would be an effective strategy to increase sample sizes to further investigate how gene variants impact the pharmacodynamics and pharmacokinetics of psychotropic drugs in elderly persons.</p> <p>PMID: 20860469 [PubMed - indexed for MEDLINE]</p>

2011-02-17T03:23:04Z PubMed:20860457

<p><b>Pharmacogenomic strategies against microbial resistance: from bright to bleak to innovative.</b></p> <p>Pharmacogenomics. 2010 Sep;11(9):1193-6</p> <p>Authors: Dandekar T, Dandekar G</p> <p>The last decade saw an alarming increase in antibiotic resistance in infections, with more than 13 million deaths per year from infections. Counter strategies include hygiene, antibiotic restriction and new antibiotics such as quinupristin, linezolid, tigecycline, daptomycin and dalbavancin. Presently, pharmacogenomics with basic research is revealing new antimicrobial peptides and is applying old drugs in new ways to break resistance. New approaches with host-directed drug targeting emerge to circumvent resistance. A future systems perspective from large-scale molecular techniques and bioinformatic modeling allows pharmacogenomics to reveal new intervention angles. This includes the fight against resistance and its transmission, improved vaccines, disarmament of microbes and antibiotic options from novel molecular targets (lipids, RNA and carbohydrates). Such a system perspective is also essential for improved diagnostics and individualized medicine. However, an increase in public awareness and closer cooperation of industry and basic research are essential to turn research into powerful new drugs that will enable us to treat new arising infections in the future.</p> <p>PMID: 20860457 [PubMed - indexed for MEDLINE]</p>

2011-02-17T03:23:04Z PubMed:20860458

<p><b>First results of largest study of genomes and cancer treatments available.</b></p> <p>Pharmacogenomics. 2010 Sep;11(9):1197-8</p> <p>Authors: </p> <p></p> <p>PMID: 20860458 [PubMed - indexed for MEDLINE]</p>

2011-02-17T03:23:04Z PubMed:20860455

<p><b>Influence of mtDNA genetic variation on antibiotic therapy.</b></p> <p>Pharmacogenomics. 2010 Sep;11(9):1185-7</p> <p>Authors: Pacheu-Grau D, Gómez-Durán A, Montoya J, Ruiz-Pesini E</p> <p></p> <p>PMID: 20860455 [PubMed - indexed for MEDLINE]</p>

2011-02-17T03:23:03Z PubMed:20860467

<p><b>Pharmacogenomics and active surveillance for serious adverse drug reactions in children.</b></p> <p>Pharmacogenomics. 2010 Sep;11(9):1269-85</p> <p>Authors: Loo TT, Ross CJ, Sistonen J, Visscher H, Madadi P, Koren G, Hayden MR, Carleton BC</p> <p>Juxtaposing clinical pharmacology with human genetics, pharmacogenomics utilizes a patient's genetic information to identify genetic variants that have the potential to provide clinically relevant predictions of toxicity and efficacy. The goal is to develop personalized and genetic-based predictions of an individual's drug response and likelihood of experiencing an adverse drug reaction. The Canadian Pharmacogenomics Network for Drug Safety (CPNDS) has implemented active adverse drug reaction surveillance to monitor and discover genetic markers related to serious adverse drug reactions in the pediatric population. Evidence-based pharmacogenomics research will inform public policy and influence drug benefit-risk decision-making. Regulatory processes and future challenges in pharmacogenomics research will be discussed.</p> <p>PMID: 20860467 [PubMed - indexed for MEDLINE]</p>

2011-02-17T03:23:03Z PubMed:20860468

<p><b>Pharmacogenetics of osteoporosis-related bone fractures: moving towards the harmonization and validation of polymorphism diagnostic tools.</b></p> <p>Pharmacogenomics. 2010 Sep;11(9):1287-303</p> <p>Authors: Rojo Venegas K, Aguilera Gómez M, Eisman JA, García Sánchez A, Faus Dader MJ, Calleja Hernández MA</p> <p>Osteoporosis is one of the most common skeletal chronic conditions in developed countries, hip fracture being one of its major healthcare outcomes. There is considerable variation in the implementation of current pharmacological treatment and prevention, despite consistent recommendations and guidelines. Many studies have reported conflicting findings of genetic associations with bone density and turnover that might predict fracture risk. Moreover, it is not clear whether genetic differences exist in relation to the morbidity and efficiency of the pharmacotherapy treatments. Clinical response, including beneficial and adverse events associated with osteoporosis treatments, is highly variable among individuals. In this context, the present article intends to summarize putative candidate genes and genome-wide association studies that have been related with BMD and fracture risk, and to draw the attention to the need for pharmacogenetic methodology that could be applicable in clinical translational research after an adequate validation process. This article mainly compiles analysis of important polymorphisms in osteoporosis documented previously, and it describes the simple molecular biology tools for routine genotype acquisition. Validation of methods for the easy, fast and accessible identification of SNPs is necessary for evolving pharmacogenetic diagnostic tools in order to contribute to the discovery of clinically relevant genetic variation with an impact on osteoporosis and its personalized treatment.</p> <p>PMID: 20860468 [PubMed - indexed for MEDLINE]</p>

2011-02-17T03:23:03Z PubMed:20860470

<p><b>Pharmacogenomics instruction in US and Canadian medical schools: implications for personalized medicine.</b></p> <p>Pharmacogenomics. 2010 Sep;11(9):1331-40</p> <p>Authors: Green JS, O'Brien TJ, Chiappinelli VA, Harralson AF</p> <p>To determine the extent of pharmacogenomics instruction at US and Canadian medical schools, characterize perceptions of curricular coverage, identify curricular resources and compare responses with similar studies conducted in US pharmacy schools and British medical schools.</p> <p>PMID: 20860470 [PubMed - indexed for MEDLINE]</p>

2011-02-16T03:00:00Z http://med.stanford.edu/ism/2011/february/knee.html

A recently discovered biomarker could help doctors diagnose a common type of knee injury, according to a study confirming that a protein complex appears in patients with meniscal tears.

2011-02-13T03:23:04Z PubMed:21064136

<p><b>Methotrexate-induced subacute neurotoxicity in a child with acute lymphoblastic leukemia carrying genetic polymorphisms related to folate homeostasis.</b></p> <p>Am J Hematol. 2011 Jan;86(1):98-101</p> <p>Authors: Vagace JM, Caceres-Marzal C, Jimenez M, Casado MS, de Murillo SG, Gervasini G</p> <p>Subacute methotrexate neurotoxicity (MTX-NT) may occur days to weeks after systemic or intrathecal (IT) MTX administration and is often manifest by stroke-like symptoms. The pathogenesis of MTX-NT has mainly been associated with cerebral folate homeostasis, but the specific mechanism leading to the development of this complication is mostly unknown and is likely to be multifactorial. Most of studies aimed to determine putative genetic determinants of this syndrome have been focused on the methylenetetrahydrofolate reductase (MTHFR) C677T single nucleotide polymorphism (SNP). However, there are other functional polymorphisms that have also been identified in enzymes and transporters related to MTX and folate homeostasis. In this context, we carried out an extensive genetic analysis through the screening of 21 SNPs in 11 relevant genes in a five-year-old girl with acute lymphoblastic leukemia (ALL) who developed MTX-NT. The analysis revealed the presence of numerous genetic variants that may have accounted for the neurotoxicity observed. We discuss the putative role of MTX pharmacogenetics in the pathogenesis of MTX-NT.</p> <p>PMID: 21064136 [PubMed - indexed for MEDLINE]</p>

2011-02-13T03:23:03Z PubMed:21040287

<p><b>The pharmacogenetics of antidepressant-induced mania: a systematic review and meta-analysis.</b></p> <p>Bipolar Disord. 2010 Nov;12(7):702-6</p> <p>Authors: Daray FM, Thommi SB, Ghaemi SN</p> <p>Antidepressant-induced mania (AIM) has been associated with the serotonin-transporter-linked promoter region (5-HTTLPR) polymorphism in some studies but not in others. We conducted a meta-analysis of those studies and other studies of genetic predictors of AIM.</p> <p>PMID: 21040287 [PubMed - indexed for MEDLINE]</p>