Genetic polymorphisms associated with atorvastatin induced myalgia
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB40922 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR4704610_1.fastq.gz | Fastqsanger.gz | |||
| ERR4704610_2.fastq.gz | Fastqsanger.gz | |||
| ERR4704620_1.fastq.gz | Fastqsanger.gz | |||
| ERR4704620_2.fastq.gz | Fastqsanger.gz | |||
| ERR4704630_1.fastq.gz | Fastqsanger.gz |
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Project description:In the exon array data set, gene level analysis was performed on HepG2 cells exposed to atorvastatin. No genes were found to be statistically significantly differentially expressed upon atorvastatin treatment.
2014-04-26 | GSE57071 | GEO
Project description:Statin-induced myotoxicity (SIM) is one of the principal reasons for atorvastatin (AT) non-adherence and/or discontinuation, contributing to adverse cardiovascular outcomes. To date, the genetic mechanism of SIM is far from well-illustrated. Published data in vitro and in vivo indicated that atorvastatin lactone (ATL) is the key metabolite to induce myotoxicity. We therefore hypothesis that genetic variants increasing the formation of ATL can increase the risk to statin-induced myotoxicity. And a transcriptome-wide association study (TWAS) integrating genome wide variants and gene expression data will applied to identify expression quantitative trait loci (eQTL) associated with the formation of ATL and different bioinformatic tools will then be applied to reveal the potential causal impact of eQTLs on the formation of ATL.
2018-10-01 | GSE87592 | GEO
Project description:Rationale: Immortalized cells may exhibit important differences relative to their primary cell counterparts. Microarrays were used compare primary human umbilical vein endothelial cells (HUVECs) and the immortalized HUVEC cell line EA.hy926, in their response to inhibition of the mevalonate pathway by a HMG-CoA reductase inhibitor (atorvastatin). The effects of atorvastatin were reversed by the addition of mevalonate, to subtract non-specific changes in gene expression. Methods: Confluent cell cultures of HUVECs and EA.hy926 cells (two independent experiments in each cell type) were incubated with 1) statin-free media; 2) 10 microM atorvastatin; 3) 500 microM mevalonate; or 4) a combination of 10 microM atorvastatin and 500 microM mevalonate. All cells were harvested at 24 h. Total RNA was isolated using Trizol reagent (Invitrogen). cDNA was prepared from 10 microgram total RNA using a double-stranded cDNA synthesis kit (Life Technologies) with a T7-dT24 primer for first-strand synthesis. cRNA was synthesized from cDNA and biotinylated using the BioArray High Yield RNA Transcript Labeling Kit (Enzo Diagnostics). Twenty microgram of cRNA was fragmented by heating at 94°C for 35 min in fragmentation buffer, containing 40 mM Tris-acetate, pH 8.1, 125 mM KOAc, 30 mM MgOAc. Fifteen micrgram of fragmented cRNA, together with control cRNAs and grid alignment oligonucleotides, were hybridized overnight to GeneChip Human Genome U133A 2.0 arrays (Affymetrix) at 45°C under constant rotation. Arrays were washed and incubated with an anti-streptavidin antibody. Fluorescent signals were measured using an Agilent Gene Array Laser Scanner and analyzed with MicroArray Suite 5.0 (Affymetrix). Microarrays were scaled using default settings. Keywords: other
2005-03-29 | GSE2450 | GEO
Project description:In the exon array data set, gene level analysis was performed on HepG2 cells exposed to atorvastatin. No genes were found to be statistically significantly differentially expressed upon atorvastatin treatment. 3 control and 3 atorvastatin treated HepG2 samples were analysed. Genes with an FDRM-bM-^IM-$5% after Benjamini-Hochberg correction was considered as differentially expressed.
2014-04-26 | E-GEOD-57071 | biostudies-arrayexpress
Project description:Numerous studies report active pharmaceutical compounds detected in both wastewater effluent and surface waters. Exposure to statin drugs in general, and atorvastatin in particular, is likely to be a concern. We hypothesized that chronic exposure to low concentrations of atorvastatin in water would result in an adverse effect on production of steroids regulating growth and development of the model amphibian Xenopus laevis. To assess the potential for impacts we used three experimental assays. The FETAX assay was used to evaluate the effects of a range of doses of atorvastatin on developing embryos. A 60 day metamorphosis assay assessed the effects of aqueous atorvastatin exposure at environmentally concentrations on metamorphosing tadpoles. A 60 day chronic flow-through exposure evaluated the effects of chronic low concentrations of atorvastatin on adults. The data from the FETAX assay confirmed uptake, activity, and effect of atorvastatin in X. laevis tadpoles. The results of the 60-day flow-through exposure on metamorphosing tadpoles showed significant evidence of altered cholesterol biosynthesis. The dose-dependent increase in cyp19a1 expression also indicated that the steroidogenesis pathway was affected. The RNAseq analysis confirmed that exposure to environmentally relevant concentrations of atorvastatin does cause significant alterations to global transcriptional profiles in a manner consistent with dysregulation of the cholesterol biosynthesis pathway, both through the downregulation of many genes involved in that pathway, but also in the impacts to other, related pathways. The qPCR data for both adult males and adult females indicated only slight changes in expression with the exception that hmgcr was significantly downregulated in males, and cyp3a4 expression was significantly downregulated in females. The data we present here indicated that chronic exposure to environmentally relevant concentrations of atorvastatin does have the potential to impact early life stage frogs, particularly by altering expression of genes involved in critical molecular pathways.
2023-07-07 | GSE236279 | GEO
Project description:Abstract: Patients with metabolic syndrome are often prescribed statins to prevent development of 17 cardiovascular disease. Conversely, data on their effects on non-alcoholic steatohepatitis (NASH) 18 are lacking. We evaluated these effects by feeding APOE*3-Leiden mice a Western-type diet (WTD) 19 with or without atorvastatin to induce NASH and hepatic fibrosis. Besides the well-known plasma 20 cholesterol lowering (-30%) and anti-atherogenic effects (severe lesion size -48%), atorvastatin sig-21 nificantly reduced hepatic steatosis (-22%), the number of aggregated inflammatory cells in the liver 22 (-80%) and hepatic fibrosis (-92%) compared to WTD-fed mice. Furthermore, atorvastatin-treated 23 mice showed less immunohistochemically stained area of inflammation markers. Atorvastatin pre-24 vented accumulation of free cholesterol in the form of cholesterol crystals (-78%). Cholesterol crys-25 tals are potent inducers of the NLRP3 inflammasome pathway and atorvastatin prevented its acti-26 vation, which resulted in reduced expression of the pro-inflammatory cytokines interleukin (IL)-1β 27 (-61%) and IL-18 (-26%). Transcriptome analysis confirmed strong reducing effects of atorvastatin 28 on inflammatory mediators, including NLRP3, NFκB and TLR4. The present study demonstrates 29 that atorvastatin reduces hepatic steatosis, inflammation and fibrosis and prevents cholesterol crys-30 tal formation, thereby precluding NLRP3 inflammasome activation. This may render atorvastatin 31 treatment as an attractive approach to reduce NAFLD and prevent progression into NASH in 32 dyslipidemic patients.
2023-05-17 | GSE229188 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE24186: Atorvastatin, rosuvastatin and rifampicin effect on human primary hepatocyte transcriptome [Steroltalk platform] GSE24187: Atorvastatin, rosuvastatin and rifampicin effect on human primary hepatocyte transcriptome [Affymetrix platform] Refer to individual Series
2011-09-04 | E-GEOD-24188 | biostudies-arrayexpress
Project description:Introduction: The genetic origin of familial combined hyperlipidemia (FCH) is not well understood. We used microarray profiling of peripheral blood monocytes to search novel genes and pathways involved in FCH. Methods: Fasting plasma for determination of lipid profiles, inflammatory molecules, and adipokines was obtained and peripheral blood monocytes were isolated from male FCH patients basally and after 4 weeks of atorvastatin treatment. Sex-, age- and adiposity-matched controls were also studied. Gene expression profile was analyzed using Affymetrix Human Genome U133A 2.0 GeneChip arrays. Results: Analysis of gene expression by cDNA microarrays showed that 82 genes were differentially expressed in FCH monocytes compared to controls. Atorvastatin treatment modified the expression of 87 genes. Changes in the expression of some genes, confirmed by real time RT-PCR, (CD36, leucine-rich repeats and immunoglobulin-like domains-1, tissue factor pathway inhibitor 2, myeloid cell nuclear differentiation antigen tumor necrosis factor receptor superfamily, member 25 and CD96) may be related to a proinflammatory environment in FCH monocytes, which is partially reversed by atorvastatin. Higher plasma levels of triglycerides and free fatty acids and lower levels of adiponectin in FCH patients could also trigger changes in gene expression that atorvastatin cannot modify. Conclusions: Our results demonstrate clear differences in gene expression in FCH monocytes compared with those of matched healthy controls, some of which are influenced by atorvastatin treatment. Keywords: comparative study differential gene expression
2008-06-03 | GSE11393 | GEO
Project description:Background: In the diabetic heart the β-adrenergic response is altered partly by down-regulation of the β1-adrenoceptor, reducing its positive inotropic effect and up-regulation of the β3-adrenoceptor, increasing its negative inotropic effect. Statins have clinical benefits on morbidity and mortality in diabetic patients which are attributed to âpleiotropicâ effects. The objective of our study was to investigate the role of statin treatment on β-adrenergic dysfunction in diabetic rat cardiomyocytes. Methods: β-adrenergic responses were investigated in vivo (echocardiography) and ex vivo (left ventricular papillary muscles) in healthy and streptozotocin-induced diabetic rats, who were pre-treated or not by oral atorvastatin over 15 days (50 mg.kg-1.day-1). Micro-array analysis and immunoblotting were performed in left ventricular homogenates. Data are presented as mean percentage of baseline ± SD. Results: Atorvastatin restored the impaired positive inotropic effect of β-adrenergic stimulation in diabetic hearts compared with healthy hearts both in vivo and ex vivo but did not suppress the diastolic dysfunction of diabetes. Atorvastatin changed the RNA expression of 9 genes in the β-adrenergic pathway and corrected the protein expression of β1-adrenoceptor and β1/β3-adrenoceptor ratio, and multidrug resistance protein 4 (MRP4). Nitric oxide synthase (NOS) inhibition abolished the beneficial effects of atorvastatin on the β-adrenoceptor response. Conclusions: Atorvastatin restored the positive inotropic effect of the β-adrenoceptor stimulation in diabetic cardiomyopathy. This effect is mediated by multiple modifications in expression of proteins in the β-adrenergic signaling pathway, particularly through the NOS pathway.
2017-06-27 | E-MTAB-5594 | biostudies-arrayexpress