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Pharmacogenomics and Personalized Medicine

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https://www.readbyqxmd.com/read/29089781/pharmacogenomics-of-sickle-cell-disease-steps-toward-personalized-medicine
#1
REVIEW
Marium Husain, Amber D Hartman, Payal Desai
Sickle cell disease (SCD) is a monogenetic disease but has a wide range of phenotypic expressions. Some of these differences in phenotype can be explained by genetic polymorphisms in the human globin gene. These polymorphisms can result in different responses to typical treatment, sometimes leading to inadequate therapeutics. Research is revealing more polymorphisms, and therefore, new targets for intervention to improve outcomes in SCD. This area of pharmacogenomics is continuing to develop. We provide a brief review of the current literature on pharmacogenomics in SCD and possible targets for intervention...
2017: Pharmacogenomics and Personalized Medicine
https://www.readbyqxmd.com/read/29075133/do-cyp2c19-and-abcb1-gene-polymorphisms-and-low-cyp3a4-isoenzyme-activity-have-an-impact-on-stent-implantation-complications-in-acute-coronary-syndrome-patients
#2
Eric Rytkin, Karin B Mirzaev, Elena A Grishina, Valeriy V Smirnov, Kristina A Ryzhikova, Zhannet A Sozaeva, Michael Iu Giliarov, Denis A Andreev, Dmitriy A Sychev
AIM: The aim of this study was to determine the impact of CYP2C19 and ABCB1 gene polymorphisms and CYP3A4 isoenzyme activity on stent implantation complications among patients with an acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI). PATIENTS AND METHODS: Seventy-six patients (median age 63, range 37-91 years) with an ACS who underwent PCI were screened for CYP2C19 and ABCB1 gene polymorphisms with real-time polymerase chain reaction: CYP2C19*2, CYP2C19*17, and ABCB1 3435...
2017: Pharmacogenomics and Personalized Medicine
https://www.readbyqxmd.com/read/29033601/urine-metabolic-ratio-of-omeprazole-in-relation-to-cyp2c19-polymorphisms-in-russian-peptic-ulcer-patients
#3
Natalia P Denisenko, Dmitriy A Sychev, Zhanna M Sizova, Valeriy V Smirnov, Kristina A Ryzhikova, Zhannet A Sozaeva, Elena A Grishina
BACKGROUND: CYP2C19 is known to be the main enzyme of biotransformation of proton pump inhibitors (PPIs), whereas the CYP2C19 gene is highly polymorphic. Genotyping and phenotyping together represent more reliable data about patient's CYP2C19 activity. PURPOSE: The aim of the study was to investigate the applicability of urine metabolic ratio of omeprazole for CYP2C19 phenotyping in Russian peptic ulcer patients with different CYP2C19 genotypes. PATIENTS AND METHODS: A total of 59 patients (19 men and 40 women) aged 18-91 years (mean age 53...
2017: Pharmacogenomics and Personalized Medicine
https://www.readbyqxmd.com/read/29026329/pharmacogenomic-testing-aiding-in-the-management-of-psychotropic-therapy-for-adolescents-with-autism-spectrum-disorders
#4
Seuli Bose-Brill, Jinming Xing, Debra J Barnette, Christopher Hanks
Adolescents with autism have higher rates of anxiety than the general adolescent population. They often struggle to express psychological symptoms verbally where their symptoms may manifest as withdrawal and agitation. Adolescent patients with autism have higher rates of polypharmacy and high-risk psychiatric medication use (eg, atypical antipsychotics) than other patients with psychiatric illness. Primary care pediatricians are at the front lines of psychiatric management for patients with autism. Yet, they have inadequate access to pediatric psychiatry for complex medication management...
2017: Pharmacogenomics and Personalized Medicine
https://www.readbyqxmd.com/read/28919802/abcb1-and-abcc1-single-nucleotide-polymorphisms-in-patients-treated-with-clozapine
#5
Irina Piatkov, Dorgival Caetano, Yolinda Assur, Sue Lynn Lau, Trudi Jones, Steven C Boyages, Mark McLean
Clozapine (CZ) has superior efficacy to other antipsychotic agents in the treatment of schizophrenia and has been extensively used in clinical practice. ATP-binding cassette (ABC) transporter proteins are responsible for the distribution of various molecules as well as drugs across extracellular and intracellular membranes, including the blood-brain barrier. Genetic variations in these proteins can account for differences in treatment response. We investigated the influence of ABCB1 rs1045642 and ABCC1 rs212090 single-nucleotide polymorphisms (SNPs) on CZ serum level, clinical outcome, and changes in body mass index (BMI) in the first year of CZ treatment...
2017: Pharmacogenomics and Personalized Medicine
https://www.readbyqxmd.com/read/28883739/hyperbilirubinemia-in-atazanavir-treated-human-immunodeficiency-virus-infected-patients-the-impact-of-the-ugt1a1-28-allele
#6
COMMENT
Anushka Naidoo, Kogieleum Naidoo, Veron Ramsuran, Millidhashni Reddy, Nesri Padayatchi
No abstract text is available yet for this article.
2017: Pharmacogenomics and Personalized Medicine
https://www.readbyqxmd.com/read/28860839/updating-the-landscape-of-direct-to-consumer-pharmacogenomic-testing
#7
REVIEW
Kelly K Filipski, John D Murphy, Kathy J Helzlsouer
Pharmacogenomics has identified important drug-gene interactions that affect the safety and efficacy of medications. Direct-to-consumer genetic testing, when first introduced, included some pharmacogenomic-related genes. The current landscape of pharmacogenomic direct-to-consumer testing is reviewed. Prior published reviews of the literature were updated through February 2017 and a scan of the current availability of direct-to-consumer genomic testing by companies was conducted. Results of the review demonstrate a shift toward physician-approved ordering...
2017: Pharmacogenomics and Personalized Medicine
https://www.readbyqxmd.com/read/28790862/hyperbilirubinemia-in-atazanavir-treated-hiv-infected-patients-the-impact-of-the-ugt1a1-28-allele
#8
REVIEW
Periklis Panagopoulos, Efstathios Maltezos, Angelos Hatzakis, Dimitrios Paraskevis
Combination antiretroviral treatment (cART) has significantly improved the life expectancy of people living with HIV. The life-long nature of cART increases the risk of side effects, which in some cases may have been caused by specific genetic characteristics. Patients treated with atazanavir (ATV) boosted with ritonavir (rit), which is a protease inhibitor used for the treatment of HIV, present with elevated bilirubin levels, at high proportions. ATV/rit-related hyperbilirubinemia has been previously associated with genetic characteristics in uridine diphosphate glucuronosyltransferase (UGT) enzyme...
2017: Pharmacogenomics and Personalized Medicine
https://www.readbyqxmd.com/read/28769582/cyp2d6-phenotypes-are-associated-with-adverse-outcomes-related-to-opioid-medications
#9
Jennifer L St Sauver, Janet E Olson, Veronique L Roger, Wayne T Nicholson, John L Black, Paul Y Takahashi, Pedro J Caraballo, Elizabeth J Bell, Debra J Jacobson, Nicholas B Larson, Suzette J Bielinski
BACKGROUND: Variation in the CYP2D6 gene may affect response to opioids in both poor and ultrarapid metabolizers, but data demonstrating such associations have been mixed, and the impact of variants on toxicity-related symptoms (e.g., nausea) is unclear. Therefore, we examined the association between CYP2D6 phenotype and poor pain control or other adverse symptoms related to the use of opioids in a sample of primary care patients. MATERIALS AND METHODS: We identified all patients in the Mayo Clinic RIGHT Protocol who were prescribed an opioid medication between July 01, 2013 and June 30, 2015, and categorized patients into three phenotypes: poor, intermediate to extensive, or ultrarapid CYP2D6 metabolizers...
2017: Pharmacogenomics and Personalized Medicine
https://www.readbyqxmd.com/read/28744152/pharmacodynamic-genetic-polymorphisms-affect-adverse-drug-reactions-of-haloperidol-in-patients-with-alcohol-use-disorder
#10
Mikhail Sergeevich Zastrozhin, Vadim Markovich Brodyansky, Valentin Yurievich Skryabin, Elena Anatolievna Grishina, Dmitry Vladimirovich Ivashchenko, Kristina Anatolievna Ryzhikova, Ludmila Mikhaylovna Savchenko, Alexander Olegovich Kibitov, Evgeny Alekseevich Bryun, Dmitry Alekseevich Sychev
BACKGROUND: Antipsychotic action of haloperidol is due to blockade of D2 receptors in the mesolimbic dopamine pathway, while the adverse drug reactions are associated with striatal D2 receptor blockade. Contradictory data concerning the effects of genetic polymorphisms of genes encoding these receptors and associated structures (catechol-O-methyltransferase [COMT], glycine transporter and gene encoding the density of D2 receptors on the neuronal membrane) are described. OBJECTIVE: The objectives of this study were to evaluate the correlation between DRD2, SLC6A3 (DAT) and COMT genetic polymorphisms and to investigate their effect on the development of adverse drug reactions in patients with alcohol-use disorder who received haloperidol...
2017: Pharmacogenomics and Personalized Medicine
https://www.readbyqxmd.com/read/28603427/pharmacogenetics-in-inflammatory-bowel-disease-understanding-treatment-response-and-personalizing-therapeutic-strategies
#11
REVIEW
Jesús K Yamamoto-Furusho
Inflammatory bowel disease (IBD) is a chronic and heterogeneous disorder characterized by remitting and relapsing periods of activity. Pharmacogenetics refers to the study of the effect of inheritance on individual variation in drug responses. Several drug-related markers in IBD patients have been identified in order to predict the response to medical treatment including biological therapy as well as the reduction of adverse events. In the future, the treatment of IBD should be personalized in its specific profile to provide the most efficacious treatment with lack of adverse events...
2017: Pharmacogenomics and Personalized Medicine
https://www.readbyqxmd.com/read/28572737/observational-study-to-calculate-addictive-risk-to-opioids-a-validation-study-of-a-predictive-algorithm-to-evaluate-opioid-use-disorder
#12
Ashley Brenton, Steven Richeimer, Maneesh Sharma, Chee Lee, Svetlana Kantorovich, John Blanchard, Brian Meshkin
BACKGROUND: Opioid abuse in chronic pain patients is a major public health issue, with rapidly increasing addiction rates and deaths from unintentional overdose more than quadrupling since 1999. PURPOSE: This study seeks to determine the predictability of aberrant behavior to opioids using a comprehensive scoring algorithm incorporating phenotypic risk factors and neuroscience-associated single-nucleotide polymorphisms (SNPs). PATIENTS AND METHODS: The Proove Opioid Risk (POR) algorithm determines the predictability of aberrant behavior to opioids using a comprehensive scoring algorithm incorporating phenotypic risk factors and neuroscience-associated SNPs...
2017: Pharmacogenomics and Personalized Medicine
https://www.readbyqxmd.com/read/28553132/cyp2c19-2-status-in-patients-with-stevens-johnson-syndrome-and-toxic-epidermal-necrolysis
#13
Amanda J Laska, Marie J Han, Josh A Lospinoso, Patrick J Brown, Thomas M Beachkofsky
PURPOSE: Genetic polymorphisms have been linked to an increased predisposition to developing certain diseases. For example, patients of Han-Chinese descent carrying the HLA-B*1502 allele are at an increased risk of developing Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) if given carbamazepine. Given the complexity of in vivo drug metabolism, it is plausible that the activity of enzyme systems unrelated to specific drug metabolism may be important. Although multiple biomarkers have been identified in unique ethnic groups, there has yet to be a study investigating the presence of the slow metabolizing allele of CYP2C19, denoted CYP2C19*2, in diverse groups and the risk of developing SJS/TEN...
2017: Pharmacogenomics and Personalized Medicine
https://www.readbyqxmd.com/read/28546766/abcb1-genetic-variants-in-leukemias-current-insights-into-treatment-outcomes
#14
REVIEW
Ravindran Ankathil
Despite improvements in treatment of different types of leukemia, not all patients respond optimally for a particular treatment. Some treatments will work better for some, while being harmful or ineffective for others. This is due to genetic variation in the form of single-nucleotide polymorphisms (SNPs) that affect gene expression or function and cause inherited interindividual differences in the metabolism and disposition of drugs. Drug transporters are one of the determinants governing the pharmacokinetic profile of chemotherapeutic drugs...
2017: Pharmacogenomics and Personalized Medicine
https://www.readbyqxmd.com/read/28533693/dna-methylation-at-the-mu-1-opioid-receptor-gene-oprm1-promoter-predicts-preoperative-acute-and-chronic-postsurgical-pain-after-spine-fusion
#15
Vidya Chidambaran, Xue Zhang, Lisa J Martin, Lili Ding, Matthew T Weirauch, Kristie Geisler, Bobbie L Stubbeman, Senthilkumar Sadhasivam, Hong Ji
INTRODUCTION: The perioperative pain experience shows great interindividual variability and is difficult to predict. The mu-1 opioid receptor gene (OPRM1) is known to play an important role in opioid-pain pathways. Since deoxyribonucleic acid (DNA) methylation is a potent repressor of gene expression, DNA methylation was evaluated at the OPRM1 promoter, as a predictor of preoperative, acute, and chronic postsurgical pain (CPSP). METHODS: A prospective observational cohort study was conducted in 133 adolescents with idiopathic scoliosis undergoing spine fusion under standard protocols...
2017: Pharmacogenomics and Personalized Medicine
https://www.readbyqxmd.com/read/28507448/thiopurine-s-methyltransferase-polymorphisms-in-acute-lymphoblastic-leukemia-inflammatory-bowel-disease-and-autoimmune-disorders-influence-on-treatment-response
#16
REVIEW
Rachid Abaji, Maja Krajinovic
The thiopurine S-methyltransferase (TPMT) gene encodes for the TPMT enzyme that plays a crucial role in the metabolism of thiopurine drugs. Genetic polymorphisms in this gene can affect the activity of the TPMT enzyme and have been correlated with variability in response to treatment with thiopurines. Advances in the pharmacogenetics of TPMT allowed the development of dosing recommendations and treatment strategies to optimize and individualize prescribing thiopurine in an attempt to enhance treatment efficacy while minimizing toxicity...
2017: Pharmacogenomics and Personalized Medicine
https://www.readbyqxmd.com/read/28461764/abcg2-polymorphisms-in-gout-insights-into-disease-susceptibility-and-treatment-approaches
#17
REVIEW
M C Cleophas, L A Joosten, L K Stamp, N Dalbeth, O M Woodward, Tony R Merriman
As a result of the association of a common polymorphism (rs2231142, Q141K) in the ATP-binding cassette G2 (ABCG2) transporter with serum urate concentration in a genome-wide association study, it was revealed that ABCG2 is an important uric acid transporter. This review discusses the relevance of ABCG2 polymorphisms in gout, possible etiological mechanisms, and treatment approaches. The 141K ABCG2 urate-increasing variant causes instability in the nucleotide-binding domain, leading to decreased surface expression and function...
2017: Pharmacogenomics and Personalized Medicine
https://www.readbyqxmd.com/read/28458572/pharmacogenetic-testing-revisited-5-nuclease-real-time-polymerase-chain-reaction-test-panels-for-genotyping-cyp2d6-and-cyp2c19
#18
Jens Borggaard Larsen, Jan Borg Rasmussen
Due to their involvement in the metabolization of commonly prescribed psychopharmaceutical drugs, the cytochrome oxidase genes CYP2D6 and CYP2C19 are extensive targets for pharmacogenetic testing. The existence of common allelic variants allows the prediction of a metabolic phenotype based on a genotype result, hereby supplying a clinical tool for optimizing prescription and minimizing adverse effects. In this study, we present the development of two 5' nuclease real-time polymerase chain reaction (PCR) test panels, capable of detecting eight of the most clinically relevant alleles of the CYP2D6 gene (*2, *3, *4, *6, *9, *10, 17, *41) and the three most common nonfunctional alleles of CYP2C19 (*2, *3, *4)...
2017: Pharmacogenomics and Personalized Medicine
https://www.readbyqxmd.com/read/28442925/cyp2c19-polymorphism-frequency-in-russian-patients-in-central-russia-and-siberia-with-acute-coronary-syndrome
#19
Karin B Mirzaev, Elena M Zelenskaya, Olga L Barbarash, Vladimir I Ganyukov, Konstantin A Apartsin, Natalya O Saraeva, Konstantin Y Nikolaev, Kristina A Ryzhikova, Galina I Lifshits, Dmitry A Sychev
PURPOSE: The aim of this study is to investigate the frequency of CYP2C19*2, *3 allelic variants, associated with poor response to clopidogrel, and CYP2C19*17, associated with excessive response to clopidogrel, in patients with acute coronary syndrome (ACS) from Siberia and Moscow regions of Russia. PATIENTS AND METHODS: The study included 512 ACS patients who were subsequently treated with coronary arterial stenting. The subjects assigned were from the cities of Central (Novosibirsk, Kemerovo), Eastern (Irkutsk), Northern (Surgut) Siberia regions and from Moscow region...
2017: Pharmacogenomics and Personalized Medicine
https://www.readbyqxmd.com/read/28435308/association-of-the-ppp3ca-c-249g-a-variant-with-clinical-outcomes-of-tacrolimus-based-therapy-in-kidney-transplant-recipients
#20
Patricia C Salgado, Fabiana Dv Genvigir, Claudia R Felipe, Helio Tedesco-Silva, Jose O Medina-Pestana, Sonia Q Doi, Mario H Hirata, Rosario Dc Hirata
BACKGROUND: The effects of genetic variants related to the pharmacodynamic mechanisms of immunosuppressive drugs on their therapeutic efficacy and safety have been poorly explored. This study was performed to investigate the influence of the PPP3CA c.249G>A variant on the clinical outcomes of kidney transplant recipients. PATIENTS AND METHODS: A total of 148 Brazilian patients received tacrolimus (TAC)-based immunosuppressive therapy for 90 days post-kidney transplantation...
2017: Pharmacogenomics and Personalized Medicine
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