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https://www.readbyqxmd.com/read/28067828/pharmacogenetic-foundations-of-therapeutic-efficacy-and-adverse-events-of-statins
#1
REVIEW
Elena Arrigoni, Marzia Del Re, Leonardo Fidilio, Stefano Fogli, Romano Danesi, Antonello Di Paolo
BACKGROUND: In the era of precision medicine, more attention is paid to the search for predictive markers of treatment efficacy and tolerability. Statins are one of the classes of drugs that could benefit from this approach because of their wide use and their incidence of adverse events. METHODS: Literature from PubMed databases and bibliography from retrieved publications have been analyzed according to terms such as statins, pharmacogenetics, epigenetics, toxicity and drug-drug interaction, among others...
January 6, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28049954/no-effect-of-slco1b1-and-cyp3a4-5-polymorphisms-on-the-pharmacokinetics-and-pharmacodynamics-of-ticagrelor-in-healthy-chinese-male-subjects
#2
Mupeng Li, Yaodong Hu, Huilan Li, Zhipeng Wen, Xiaolei Hu, Daoyu Zhang, Yanjiao Zhang, Jian Xiao, Jie Tang, Xiaoping Chen
Ticagrelor is a direct-acting P2Y12 receptor antagonist. It is rapidly absorbed and partly metabolized to the active metabolite AR-C124910XX by CYP3A4 and CYP3A5. Three genetic loci (SLCO1B1, CYP3A4, and UGT2B7) were reported to affect ticagrelor pharmacokinetics. This study aimed to investigate the possible effects of SLCO1B1 and CYP3A4/5 genetic polymorphisms on the pharmacokinetics and pharmacodynamics of ticagrelor in healthy Chinese male volunteers. Eighteen healthy male volunteers who participated in pharmacogenetics study of ticagrelor were genotyped for SLCO1B1 rs113681054, SLCO1B1*5 (rs4149056), CYP3A4*1G (rs2242480), and CYP3A5*3 (rs776746)...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/27977017/effect-of-genetic-variants-of-bilirubin-metabolism-on-the-degree-of-hyperbilirubinemia-in-african-american-newborns
#3
D L Schutzman, L M Baudhuin, E Gatien, S Ajayi, R J Wong
OBJECTIVE: The objective of our study was to measure the effect of genetic variants of these two enzymes, UGT1A1 and SLCO1B1, in the bilirubin metabolic pathway on the degree of hyperbilirubinemia in a cohort of African-American (AA) infants from our well-baby nursery. In addition, a second objective was to document the types and frequencies of genetic variations of these enzymes in our cohort. STUDY DESIGN: A prospective study of 180 AA infants from the Well Baby Nursery of an inner city community hospital, all of whose mothers were type O pos...
December 15, 2016: Journal of Perinatology: Official Journal of the California Perinatal Association
https://www.readbyqxmd.com/read/27967318/effect-of-polymorphisms-in-cyp3a4-ppara-nr1i2-nfkb1-abcg2-and-slco1b1-on-the-pharmacokinetics-of-lovastatin-in-healthy-chinese-volunteers
#4
Guilian Zhao, Mei Liu, Xiujun Wu, Guofei Li, Feng Qiu, Jingkai Gu, Limei Zhao
AIM: This study examined whether gene polymorphisms (CYP3A4, ABCG2, SLCO1B1, NR1I2, PPARA and NFKB1) influenced the pharmacokinetics of lovastatin in Chinese healthy subjects. PATIENTS & METHOD: Plasma concentrations of lovastatin and lovastatin acid were quantified using LC/MS/MS. RESULTS: PPARA c.208+3819 G allele carriers had approximately twofold higher AUC0-∞ and Cmax of lovastatin than wild-type (PPARA c.208+3819 AA) subjects. After adjustment for the PPARA variants, subjects with the SLCO1B1 521TT genotype had approximately 50% lower AUC0-∞ of lovastatin acid than those with 521TC/CC genotypes, while the AUC0-∞ of lovastatin lactone in NFKB1-94 DD wild-type carriers was twofold higher than in mutant homozygotes carriers...
January 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/27936281/interindividual-and-interethnic-variability-in-drug-disposition-mt%C3%A2-%C3%A2-polymorphisms-in-organic-anion-transporting-polypeptide-1b1-oatp1b1-slco1b1
#5
REVIEW
Hannah H Lee, Richard H Ho
OATP1B1 (SLCO1B1) is predominantly expressed at the basolateral membrane of hepatocytes and is critically important for the hepatic uptake and clearance of numerous drug substrates and endogenous compounds. In general, the organic anion transporting polypeptides (OATP; SLCO) represent a superfamily of uptake transporters that mediate the sodium-independent transport of a diverse range of amphipathic organic compounds including bile salts, steroid conjugates, thyroid hormones, anionic peptides, numerous drugs and other xenobiotic substances...
December 9, 2016: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/27897269/an-integrated-pharmacokinetic-pharmacogenomic-analysis-of-abcb1-and-slco1b1-polymorphisms-on-edoxaban-exposure
#6
A G Vandell, J Lee, M Shi, I Rubets, K S Brown, J R Walker
Edoxaban and its low-abundance, active metabolite M4 are substrates of P-glycoprotein (P-gp; MDR1) and organic anion transporter protein 1B1 (OATP1B1), respectively, and pharmacological inhibitors of P-gp and OATP1B1 can affect edoxaban and M4 pharmacokinetics (PK). In this integrated pharmacogenomic analysis, genotype and concentration-time data from 458 healthy volunteers in 14 completed phase 1 studies were pooled to examine the impact on edoxaban PK parameters of allelic variants of ABCB1 (rs1045642: C3435T) and SLCO1B1 (rs4149056: T521C), which encode for P-gp and OATP1B1...
November 29, 2016: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/27826798/contribution-of-pharmacogenetic-testing-to-modeled-medication-change-recommendations-in-a-long-term-care-population-with-polypharmacy
#7
Elaine A Sugarman, Ali Cullors, Joel Centeno, David Taylor
BACKGROUND: Among long-term care facility residents, polypharmacy is common, and often appropriate, given the need to treat multiple, complex, chronic conditions. Polypharmacy has, however, been associated with increased healthcare costs, adverse drug events, and drug interactions. The current study evaluates the potential medication cost savings of adding personalized pharmacogenetic information to traditional medication management strategies. METHODS: One hundred and twelve long-term care residents completed pharmacogenetic testing for targeted variants in the following genes: CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4/CYP3A5, HTR2A, HTR2C, SLC6A4, SLC6A2 COMT, OPRM1, SLCO1B1, VKORC1 and MTHFR...
December 2016: Drugs & Aging
https://www.readbyqxmd.com/read/27825144/genetic-variants-associated-with-gastrointestinal-symptoms-in-fabry-disease
#8
Maria Teresa Di Martino, Francesca Scionti, Simona Sestito, Angela Nicoletti, Mariamena Arbitrio, Pietro Hiram Guzzi, Valentina Talarico, Federica Altomare, Maria Teresa Sanseviero, Giuseppe Agapito, Antonio Pisani, Eleonora Riccio, Osvaldo Borrelli, Daniela Concolino, Licia Pensabene
Gastrointestinal symptoms (GIS) are often among the earliest presenting events in Fabry disease (FD), an X-linked lysosomal disorder caused by the deficiency of α-galactosidase A. Despite recent advances in clinical and molecular characterization of FD, the pathophysiology of the GIS is still poorly understood. To shed light either on differential clinical presentation or on intervariability of GIS in FD, we genotyped 1936 genetic markers across 231 genes that encode for drug-metabolizing enzymes and drug transport proteins in 49 FD patients, using the DMET Plus platform...
November 5, 2016: Oncotarget
https://www.readbyqxmd.com/read/27812757/counter-flow-suggests-transport-of-dantrolene-and-5-oh-dantrolene-by-the-organic-anion-transporters-2-oat2-and-3-oat3
#9
Birgitta C Burckhardt, Maja Henjakovic, Yohannes Hagos, Gerhard Burckhardt
Dantrolene is the only available drug for the treatment of malignant hyperthermia, a life-threatening inborn sensitivity of the ryanodine receptor (RyR1) in skeletal muscles to volatile anesthetics. Dantrolene is metabolized in the liver to 5-OH dantrolene. Both compounds are zwitterions or net negatively charged. Here, we investigated interactions of dantrolene and 5-OH dantrolene with solute carrier (SLC) family members occurring in skeletal muscle cells, hepatocytes, and renal proximal tubule cells. SLC22A8 (organic anion transporter 3, OAT3) was very sensitive to both compounds exhibiting IC50 values of 0...
November 2016: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/27807988/rationale-and-design-of-the-slco1b1-genotype-guided-statin-therapy-trial
#10
Kavisha Singh, Bruce Peyser, Gloria Trujillo, Nicholas Milazzo, Dillon Savard, Susanne B Haga, Michael Musty, Deepak Voora
No abstract text is available yet for this article.
November 3, 2016: Pharmacogenomics
https://www.readbyqxmd.com/read/27787353/modelling-of-atorvastatin-pharmacokinetics-and-the-identification-of-the-effect-of-a-bcrp-polymorphism-in-the-japanese-population
#11
Nikolaos Tsamandouras, Yingying Guo, Thierry Wendling, Stephen Hall, Aleksandra Galetin, Leon Aarons
AIM: Ethnicity plays a modulating role in atorvastatin pharmacokinetics (PK), with Asian patients reported to have higher exposure compared with Caucasians. Therefore, it is difficult to safely extrapolate atorvastatin PK data and models across ethnic groups. This work aims to develop a population PK model for atorvastatin and its pharmacologically active metabolites specifically for the Japanese population. Subsequently, it aimed to identify genetic polymorphisms affecting atorvastatin PK in this population...
January 2017: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/27757045/pharmacogenomics-of-statins-understanding-susceptibility-to-adverse-effects
#12
Joseph P Kitzmiller, Eduard B Mikulik, Anees M Dauki, Chandrama Murkherjee, Jasmine A Luzum
Statins are a cornerstone of the pharmacologic treatment and prevention of atherosclerotic cardiovascular disease. Atherosclerotic disease is a predominant cause of mortality and morbidity worldwide. Statins are among the most commonly prescribed classes of medications, and their prescribing indications and target patient populations have been significantly expanded in the official guidelines recently published by the American and European expert panels. Adverse effects of statin pharmacotherapy, however, result in significant cost and morbidity and can lead to nonadherence and discontinuation of therapy...
2016: Pharmacogenomics and Personalized Medicine
https://www.readbyqxmd.com/read/27636550/a-european-spectrum-of-pharmacogenomic-biomarkers-implications-for-clinical-pharmacogenomics
#13
Clint Mizzi, Eleni Dalabira, Judit Kumuthini, Nduna Dzimiri, Istvan Balogh, Nazli Başak, Ruwen Böhm, Joseph Borg, Paola Borgiani, Nada Bozina, Henrike Bruckmueller, Beata Burzynska, Angel Carracedo, Ingolf Cascorbi, Constantinos Deltas, Vita Dolzan, Anthony Fenech, Godfrey Grech, Vytautas Kasiulevicius, Ľudevít Kádaši, Vaidutis Kučinskas, Elza Khusnutdinova, Yiannis L Loukas, Milan Macek, Halyna Makukh, Ron Mathijssen, Konstantinos Mitropoulos, Christina Mitropoulou, Giuseppe Novelli, Ioanna Papantoni, Sonja Pavlovic, Giuseppe Saglio, Jadranka Setric, Maja Stojiljkovic, Andrew P Stubbs, Alessio Squassina, Maria Torres, Marek Turnovec, Ron H van Schaik, Konstantinos Voskarides, Salma M Wakil, Anneke Werk, Maria Del Zompo, Branka Zukic, Theodora Katsila, Ming Ta Michael Lee, Alison Motsinger-Rief, Howard L Mc Leod, Peter J van der Spek, George P Patrinos
Pharmacogenomics aims to correlate inter-individual differences of drug efficacy and/or toxicity with the underlying genetic composition, particularly in genes encoding for protein factors and enzymes involved in drug metabolism and transport. In several European populations, particularly in countries with lower income, information related to the prevalence of pharmacogenomic biomarkers is incomplete or lacking. Here, we have implemented the microattribution approach to assess the pharmacogenomic biomarkers allelic spectrum in 18 European populations, mostly from developing European countries, by analyzing 1,931 pharmacogenomics biomarkers in 231 genes...
2016: PloS One
https://www.readbyqxmd.com/read/27631194/mapping-slco1b1-genetic-variation-for-global-precision-medicine-in-understudied-regions-in-africa-a-focus-on-zulu-and-cape-admixed-populations
#14
Nisreen Hoosain, Brendon Pearce, Clifford Jacobs, Mongi Benjeddou
The U.S. President Barack Obama has announced, in his State of the Union address on January 20, 2015, the Precision Medicine Initiative, a US$215-million program. For global precision medicine to become a reality, however, biological and environmental "variome" in previously understudied populations ought to be mapped and catalogued. Chief among the molecular targets that warrant global mapping is the organic anion-transporting polypeptide 1B1 (OATP1B1), encoded by solute carrier organic anion transporter family member 1B1 (SLCO1B1), a hepatic uptake transporter predominantly expressed in the basolateral side of hepatocytes...
September 2016: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/27631193/slco1b1-gene-variations-among-tanzanians-ethiopians-and-europeans-relevance-for-african-and-worldwide-precision-medicine
#15
Eleni Aklillu, Abiy Habtewold, Eliford Ngaimisi, Getnet Yimer, Sabina Mugusi, Wondwossen Amogne, Tasmin Reuter, Andreas Meid, Michael Marcus Hoffmann, Johanna Weiss
The solute carrier organic anion transporter family member 1B1 (SLCO1B1) gene encodes for a membrane-bound organic anion transporter protein involved in active cellular influx of many endogenous compounds and xenobiotics. SLCO1B1 genetic variation is associated, for example, with highly variable rifampicin exposure, thus influencing the cornerstone antituberculosis therapy, especially in sub-Saharan Africa where it is a key therapeutic modality. Yet, there is no SLCO1B1-guided pharmacogenetic dosing recommendation for rifampicin to reduce the risk of adverse events or therapy failure...
September 2016: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/27631189/pharmacogenomics-of-rosuvastatin-a-glocal-global-local-african-perspective-and-expert-review-on-a-statin-drug
#16
Nyarai D Soko, Collen Masimirembwa, Collet Dandara
The incidence of cardiovascular diseases (CVDs) in African populations residing in the African continent is on the rise fueled by both a steady increase in CVD risk factors and comorbidities such as human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS), tuberculosis, and parasitic diseases such as bilharzia. Statins are recommended together with lifestyle changes in the treatment of hypercholesterolemia and overall reduction of cardiovascular events. Rosuvastatin in particular is an attractive candidate in the management of CVDs in African populations often plagued with multimorbidities owing to both its potency and low drug-to-drug interaction potential...
September 2016: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/27624558/the-enhanced-atorvastatin-hepatotoxicity-in-diabetic-rats-was-partly-attributed-to-the-upregulated-hepatic-cyp3a-and-slco1b1
#17
Nan Shu, Mengyue Hu, Zhaoli Ling, Peihua Liu, Fan Wang, Ping Xu, Zeyu Zhong, Binbin Sun, Mian Zhang, Feng Li, Qiushi Xie, Xiaodong Liu, Li Liu
Liver injury is a common adverse effect of atorvastatin. This study aimed to investigate atorvastatin-induced hepatotoxicity in diabetic rats induced by high-fat diet combined with streptozotocin. The results showed that 40 mg/kg atorvastatin was lethal to diabetic rats, whose mean survival time was 6.2 days. Severe liver injury also occurred in diabetic rats treated with 10 mg/kg and 20 mg/kg atorvastatin. The in vitro results indicated that atorvastatin cytotoxicity in hepatocytes of diabetic rats was more severe than normal and high-fat diet feeding rats...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27606156/association-between-slco1b1-521t-c-and-388a-g-polymorphisms-and-risk-of-statin-induced-adverse-drug-reactions-a-meta-analysis
#18
REVIEW
Jiajia Jiang, Qing Tang, Jing Feng, Rong Dai, Yang Wang, Yuan Yang, Xiaojun Tang, Changkai Deng, Huan Zeng, Yong Zhao, Fan Zhang
An increasing number of studies have investigated the association between SLCO1B1 -521T>C and -388A>G polymorphisms and the risk of statin-induced adverse drug reactions (ADRs), but the results have been inconsistent. This meta-analysis was performed to gain more insight into the relationship. PubMed, Embase, Cochrane Library and Web of Science were searched for relevant articles published before March 5th, 2015. The quality of included studies was evaluated by the Newcastle-Ottawa Quality scale. Pooled effect estimates (odds ratios [ORs] or hazard ratios [HRs) and corresponding 95 % confidence intervals (CIs) were calculated to assess the association in overall and subgroup analyses for various genetic models...
2016: SpringerPlus
https://www.readbyqxmd.com/read/27602404/loss-of-function-variants-influence-the-human-serum-metabolome
#19
Bing Yu, Alexander H Li, Ginger A Metcalf, Donna M Muzny, Alanna C Morrison, Simon White, Thomas H Mosley, Richard A Gibbs, Eric Boerwinkle
The metabolome is a collection of small molecules resulting from multiple cellular and biological processes that can act as biomarkers of disease, and African-Americans exhibit high levels of genetic diversity. Exome sequencing of a sample of deeply phenotyped African-Americans allowed us to analyze the effects of annotated loss-of-function (LoF) mutations on 308 serum metabolites measured by untargeted liquid and gas chromatography coupled with mass spectrometry. In an independent sample, we identified and replicated four genes harboring six LoF mutations that significantly affected five metabolites...
August 2016: Science Advances
https://www.readbyqxmd.com/read/27595674/statin-associated-muscle-symptoms-and-slco1b1-rs4149056-genotype-in-patients-with-familial-hypercholesterolemia
#20
Htet Khine, Wei Cheng Yuet, Beverley Adams-Huet, Zahid Ahmad
UNLABELLED: Patients with familial hypercholesterolemia (FH) may be at increased risk for statin-associated muscle symptoms because they require long-term treatment with high-intensity statin therapy. We sought to determine (1) whether other predisposing factors, including the well-known genetic variant associated with statin-associated muscle symptoms-solute carrier organic anion transporter family, member 1B1 (SLCO1B1) rs4149056-also increase the risk of statin-associated muscle symptoms in FH patients, and (2) the natural history and management for FH patients with statin-associated muscle symptoms...
September 2016: American Heart Journal
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