Pharmacogenomics of Statin Therapy (POST)
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PROVIDER: PRJNA1093553 | ENA |
REPOSITORIES: ENA
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Project description:Pharmacogenomics of Statin Therapy (POST)
| PRJNA1093552 | ENA
Project description:We performed a genome-wide association study in pooled DNA samples from patients with severe statin myopathy and persistent symptoms post-therapy versus pooled DNAs from an age-adjusted statin-tolerant group.
2010-07-09 | GSE17574 | GEO
Project description:Pharmacogenomics of Rheumatoid Arthritis Therapy
| PRJNA294477 | ENA
Project description:This experiment set is used for the manuscript entitled: Pharmacogenomics of Interferon-b therapy in multiple sclerosis: Baseline IFN signature determines pharmacological differences between patients. In this study we generated and analyzed pre- and post- IFNb treatment gene expression patterns of RRMS patients with the aim of identifying pre-existing and/or drug-induced signatures that will allow us to make predictions on the expected pharmacological effects of IFNb treatment. We show that the expression level of IFN response genes prior to treatment, determines the pharmacological differences between patients with MS at the molecular level. A group of 16 Dutch patients (10 females and 6 males) with clinically definite relapsing-remitting MS was recruited from the outpatient clinic of the MS Centre Amsterdam. Mean age at start of IFNb therapy is 40.6 +/- 7.7, mean EDSS is 2.3 +/- 1.3 (range 1-6). Blood samples were obtained just before treatment and 1 month after start of the therapy. Patients received Avonex, Betaferon, Rebif 22 or Rebif 44. A compound treatment design type is where the response to administration of a compound or chemical (including biological compounds such as hormones) is assayed. Compound Based Treatment: Before and 1 month after IFNb therapy Keywords: compound_treatment_design Complex
2008-04-01 | E-GEOD-10655 | biostudies-arrayexpress
Project description:We performed a genome-wide association study in pooled DNA samples from patients with severe statin myopathy and persistent symptoms post-therapy versus pooled DNAs from an age-adjusted statin-tolerant group. Affymetrix 100K SNP arrays were used according to the manufacturers instructions with two pools of 19 and 20 statin myopathy patients and two pools of 20 statin-tolerant controls.
2010-07-09 | E-GEOD-17574 | biostudies-arrayexpress
Project description:This experiment set is used for the manuscript entitled: Pharmacogenomics of Interferon-b therapy in multiple sclerosis: Baseline IFN signature determines pharmacological differences between patients. In this study we generated and analyzed pre- and post- IFNb treatment gene expression patterns of RRMS patients with the aim of identifying pre-existing and/or drug-induced signatures that will allow us to make predictions on the expected pharmacological effects of IFNb treatment. We show that the expression level of IFN response genes prior to treatment, determines the pharmacological differences between patients with MS at the molecular level. A group of 16 Dutch patients (10 females and 6 males) with clinically definite relapsing-remitting MS was recruited from the outpatient clinic of the MS Centre Amsterdam. Mean age at start of IFNb therapy is 40.6 +/- 7.7, mean EDSS is 2.3 +/- 1.3 (range 1-6). Blood samples were obtained just before treatment and 1 month after start of the therapy. Patients received Avonex, Betaferon, Rebif 22 or Rebif 44. A compound treatment design type is where the response to administration of a compound or chemical (including biological compounds such as hormones) is assayed. Compound Based Treatment: Before and 1 month after IFNb therapy Keywords: compound_treatment_design
2008-04-01 | GSE10655 | GEO
Project description:Statins, the 3-hydroxy-3-methyl-glutaryl (HMG)-CoA reductase inhibitors, are widely prescribed for treatment of hypercholesterolemia. Although statins are generally well tolerated, up to ten percent of patients taking statins experience muscle related adverse events. Myalgia, defined as muscle pain without elevated creatinine phosphokinase (CPK) levels, is the most frequent reason for discontinuation of statin therapy. The mechanisms underlying statin-associated myalgia are not clearly understood. To elucidate changes in gene expression associated with statin-induced myalgia, we compared profiles of gene expression in the biopsied skeletal muscle from statin-intolerant patients undergoing statin re-challenge versus those of statin-tolerant controls. A robust separation of statin-intolerant and statin-tolerant cohorts was revealed by Principal Component Analysis of differentially expressed genes (DEGs). To identify putative gene expression and metabolic pathways that may be perturbed in skeletal muscles of statin intolerant patients, we subjected DEGs to Ingenuity Pathways (IPA) and DAVID (Database for Annotation, Visualization and Integrated Discovery) analyses. The most prominent pathways altered by statins included cellular stress, apoptosis, senescence and DNA repair (TP53, BARD1, Mre11 and RAD51); activation of pro-inflammatory immune response (CXCL12, CST5, POU2F1); protein catabolism, cholesterol biosynthesis, protein prenylation and RAS-GTPase activation (FDFT1, LSS, TP53, UBD, ATF2, H-ras). Based on these data we tentatively conclude that persistent myalgia in response to statins may emanate from cellular stress underpinned by mechanisms of post-inflammatory repair and regeneration. We also posit that this subset of individuals are genetically predisposed to eliciting altered statin metabolism and/or increased end-organ susceptibility that lead to a range of statin-induced myopathies. This mechanistic scenario further bolstered by the discovery that a number of single nucleotide polymorphisms (e.g., SLCO1B1, SLCO2B1 and RYR2) associated with statin myopathy were observed with increased frequency among statin-intolerant study subjects.
2017-08-18 | GSE97254 | GEO
Project description:Statin therapy is associated with lower prevalence of gut microbiota dysbiosis
| PRJEB37249 | ENA
Project description:Statins reduce cardiovascular disease risk by lowering plasma low density lipoprotein (LDL)-cholesterol. To identify novel pathways that modulate statin response, we assessed the influence of simvastatin exposure on expression quantitative trait locus (eQTL) associations across the genome in 480 lymphoblastoid cell lines (LCLs). Cell lines were derived blood samples collected ant entry visit from participants in the Cholesterol and Pharmacogenomics (CAP) trial, who underwent a 6 week 40mg/day simvastatin trial. We identified 4590 cis-eQTLS that were independent of treatment status (FDR=1%) and six cis-eQTLS for which there was evidence of an interaction with treatment (FDR=20%). Genotypes and Phenotypes derived from these indivudals are available through dbGaP (Accession Number). eQTL results are available at: http://eqtl.uchicago.edu/cgi=bin/gbrowse/eqtl/
2012-07-01 | GSE36868 | GEO
Project description:Recent discoveries revealed HMG-CoA is a reactive metabolite that can non-enzymatically modify proteins and impact their activity. Therefore, we predicted that inhibition of HMGCR by statins might increase HMG-CoA levels and protein modifications. Upon statin treatment, we observed a strong increase in HMG-CoA levels, and only a single protein was modified. Mass spectrometry revealed fatty acid synthase (FAS) was modified on active site residues and, importantly, the modification is located on non-lysine side-chains.
2022-05-20 | PXD030952 | Pride