Plasma miRNA profiles associated with stable warfarin dosage in Chinese patients.
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ABSTRACT:
SUBMITTER: Zhao L
PROVIDER: S-EPMC7566751 | biostudies-literature | 2020
REPOSITORIES: biostudies-literature
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Project description:ObjectiveTo investigate the association between DNA methylation and the stable warfarin dose through genome-wide DNA methylation analysis and pyrosequencing assay.MethodThis study included 161 patients and genome-wide DNA methylation analysis was used to screen potential warfarin dose-associated CpGs through Illumina Infinium HumanMethylation 450 K BeadChip; then, the pyrosequencing assay was used to further validate the association between the stable warfarin dose and alterations in the methylation of the screened CpGs. GenomeStudio Software and R were used to analyze the differentially methylated CpGs.ResultsThe methylation levels of CpGs surrounding the xenobiotic response element (XRE) within the CYP1A1 promoter, differed significantly between the different dose groups (P < 0.05), and these CpGs presented a positive correlation (r> 0, P < 0.05) with an increase in the stable dose of warfarin. At the VKORC1 promoter, two CpGs methylation levels were significantly different between the differential dose groups (P < 0.05), and one CpG (Chr16: 31106793) presented a significant negative correlation (r < 0, P < 0.05) among different dose (low, medium, and high) groups.ConclusionThis is a novel report of the methylation levels of six CpGs surrounding the XRE within the CYP1A1 promoter and one differential CpG at the VKORC1 promoter associated with stable warfarin dosage; these methylation levels might be applied as molecular signatures for warfarin.
| S-EPMC8231338 | biostudies-literature
Project description:ObjectivesAs the most frequently prescribed anticoagulant, warfarin has large inter-individual variability in dosage. Genetic polymorphisms could largely explain the differences in dosage requirement. rs9923231 (VKORC1), rs7294 (VKORC1), rs1057910 (CYP2C9), rs2108622 (CYP4F2), and rs699664 (GGCX) involved in the warfarin action mechanism and the circulatory vitamin K were selected to investigate their polymorphism characteristics and their effects on the pharmacodynamics and pharmacokinetics of warfarin in Chinese population.Methods220 patients with cardiac valve replacement were recruited. International normalized ratio and plasma warfarin concentrations were determined. The five genetic polymorphisms were genotyping by pyro-sequencing. The relationships of maintenance dose, plasma warfarin concentration and INR were assessed among groups categorized by genotypes.Resultsrs9923231 and rs7294 in VKORC1 had the analogous genotype frequencies (D': 0.969). 158 of 220 recruited individuals had the target INR (1.5-2.5). Patients with AA of rs9923231 and CC of rs7294 required a significantly lower maintenance dose and plasma concentration than those with AG and TC, respectively. The mean weekly maintenance dose was also significantly lower in CYP2C9 rs1057910 mutated heterozygote than in patients with the wild homozygote. Eliminating the influence from environment factors (age, body weight and gender), rs9923231 and rs1057910 could explain about 32.0% of the variability in warfarin maintenance dose; rs7294 could explain 26.7% of the variability in plasma concentration. For patients with allele G of rs9923231 and allele T of rs7294, higher plasma concentration was needed to achieve the similar goal INR.ConclusionsA better understanding of the genetic variants in individuals can be the foundation of warfarin dosing algorithm and facilitate the reasonable and effective use of warfarin in Chinese.
| S-EPMC4296935 | biostudies-literature
Project description:Interstitial lung disease (ILD) is frequently associated with rheumatoid arthritis (RA), and is designated RA-associated ILD (RA-ILD). RA-ILD has a large impact on the prognosis of RA. Here, we investigated the micro RNAs (miRNAs) profiles to determine whether they may be useful for diagnosing RA-ILD.RNA was isolated from plasma samples and cDNA was synthesized. Real-time RT-PCR analysis was performed to evaluate 752 miRNA expression profiles in plasma pools from RA patients with or without RA-ILD. Sixteen selected miRNA levels were analyzed in individual plasmas from 64 RA patients with or without RA-ILD.Expression levels of hsa-miR-214-5p (mean relative expression level?±?standard deviation, 8.1?±?28.2 in RA with ILD, 0.2?±?0.9 in RA without ILD, P?=?0.0156) and hsa-miR-7-5p (56.2?±?260.4 in RA with ILD, 4.7?±?11.8 in RA without ILD, P?=?0.0362) were higher in RA patients with RA-ILD than in those without. The values of miRNA index (214, 7) generated from hsa-miR-214-5p and hsa-miR-7-5p for ILD were significantly elevated in RA patients with RA-ILD compared with those without (0.122?±?0.332 in RA with ILD, 0.006?±?0.013 in RA without ILD, P?=?0.0010). The area under the curve value of the receiver operating characteristic curve for the miRNA index (214, 7) was 0.740.To the best of our knowledge, this is the first report of miRNA profiles in RA-ILD. The expression levels of hsa-miR-214-5p and hsa-miR-7-5p were increased in RA with ILD.
| S-EPMC5244611 | biostudies-literature
Project description:Studies of miRNA association with Argonaute (AGO) proteins in mammalian cells have indicated lack of bias toward particular AGO. However, to our knowledge, the use of quantitative methods for studying miRNA association with different AGOs has not been reported so far. In this work we compared the total miRNA content in AGO1 and AGO2 immunoprecipitates obtained from MCF7 adenocarcinoma cells using TaqMan Low Density miRNA Arrays and successfully verified selected miRNAs with qPCR. For most of the miRNA species AGO1 and AGO2 profiles were well correlated, however, some miRNAs demonstrated consistent biases toward one of the Argonautes. Furthermore, miRNAs which were predominantly AGO2-associated derived mostly from sense strands of the corresponding pre-miRNAs while the majority of AGO1 biased miRNAs originated from antisense strands of the pre-miRNAs. Additionally, we show that circulating miRNA in human blood plasma can be immunoprecipitated with both AGO1 and AGO2 antibody. However, unlike in cell lysates, AGO1 and AGO2 associated miRNA profiles in plasma did not correlate, indicating that many cell types contribute to circulating miRNA (given that expression of AGO proteins is tissue specific). Furthermore, AGO-specific miRNA profiles in blood cells differed significantly from miRNAs profiles in plasma indicating that most circulating miRNAs are likely to derive from non-blood cells. Since circulating miRNAs hold great promise as biomarkers for numerous cancers and other diseases, we hypothesize that AGO-specific miRNA profiles might add an additional dimension to circulating miRNA-based diagnostics.
| S-EPMC3551861 | biostudies-other
Project description:BackgroundOvarian cancer is the fifth most common cancer in women worldwide. Moreover, there are no reliable minimal invasive tests to secure the diagnosis of malignant pelvic masses. Cell-free, circulating microRNAs have the potential as diagnostic biomarkers in cancer. Here, we performed and validated a miRNA panel with the potential to distinguish OC from benign pelvic masses.MethodsThe profile of plasma microRNA was determined with a panel of 46 candidates in a discovery group and a validation group, each consisting of 190 pre-surgery plasma samples from age-matched patients with malignant (n = 95) and benign pelvic mass (n = 95), by real time RT-qPCR.ResultsFour up-regulated (miR-200c-3p, miR-221-3p, miR-21-5p, and miR-484) and two down-regulated (miR-195-5p and miR-451a) microRNAs were discovered. From those, miR-200c-3p and miR-221-3p were further confirmed in a validation cohort. A combination of these 2 microRNAs together with CA-125 yielded an overall diagnostic accuracy of AUC = 0.96.ConclusionsWe showed consistent plasma microRNA profiles that provide independent diagnostic information of late stage OC.
| S-EPMC6860451 | biostudies-literature
Project description:The outstanding characteristics of circulatory microRNAs (miRNAs) attract much attention in research on disease biomarkers and disease pathogenesis. This study aimed to identify the expression profiles of plasma miRNAs in patients with rheumatoid arthritis (RA). Thirty-three miRNAs were screened using an miRNA array, of which 9 miRNAs were validated as differentially expressed in the plasma of RA patients compared with healthy controls (HCs). miRNA-4634 (miR-4634), miR-181d and miR-4764-5p expression levels were increased, whereas miR-342-3p, miR-3926, miR-3925-3p, miR-122-3p, miR-9-5p and miR-219-2-3p expression levels were decreased in RA patients. The areas under the curve (AUCs) were generated to estimate the sensitivity and specificity of each miRNA or the panel of all 9 miRNAs as biomarkers for RA. AUCs for 9 individual miRNAs ranged from 0.6254 to 0.818; however, the AUC for the panel of 9 miRNAs reached 0.964. Levels of miR-122-3p, miR-3925-3p, miR-342-3p and miR-4764-5p expression showed significant differences between RA and other control groups. miR-4764-5p, miR-4634, miR-9-5p and miR-219-2-3p exhibited significant correlations with either plasma cytokine and chemokine levels or clinical features. In conclusion, this study identified 9-plasma miRNAs signature in Chinese patients with RA which may serve as noninvasive biomarkers for the diagnosis of RA.
| S-EPMC4767452 | biostudies-literature
Project description:Multiple sclerosis (MS) is an autoimmune disease that leads to the demyelination of nerve axons. An increasing number of studies suggest that patients with MS exhibit altered metabolic profiles, which might contribute to the course of MS. However, the alteration of metabolic profiles in Chinese patients with MS and their potential roles in regulating the immune system remain elusive. In this study, we performed a global untargeted metabolomics approach in plasma samples from 22 MS-affected Chinese patients and 21 healthy subjects. A total of 42 differentially abundant metabolites (DAMs) belonging to amino acids, lipids, and carbohydrates were identified in the plasma of MS patients and compared with those in healthy controls. We observed an evident reduction in the levels of amino acids, such as L-tyrosine, L-isoleucine, and L-tryptophan, whereas there was a great increase in the levels of L-glutamic acid and L-valine in MS-affected patients. The levels of lipid and carbohydrate metabolites, such as sphingosine 1-phosphate and myo-inositol, were also reduced in patients with MS. In addition, the concentrations of proinflammatory cytokines, such as IL-17 and TNF-α, were significantly increased, whereas those of several anti-inflammatory cytokines and chemokines, such as IL-1ra, IL-7, and MIP-1α, were distinctly reduced in the plasma of MS patients compared with those in healthy subjects. Interestingly, some DAMs, such as L-tryptophan and sphingosine 1-phosphate, showed an evident negative correlation with changes in the level of TNF-α and IL-17, while tightly positively correlating with altered concentrations of anti-inflammatory cytokines and chemokines, such as MIP-1α and RANTES. Our results revealed that altered metabolomic profiles might contribute to the pathogenesis and course of MS disease by modulating immuno-inflammatory responses in the peripheral system, which is essential for eliciting autoimmune responses in the central nervous system, thus resulting in the progression of MS. This study provides potential clues for developing therapeutic strategies for MS in the near future.
| S-EPMC8715987 | biostudies-literature
Project description:Warfarin is the most commonly used antithrombotic drug. Single nucleotide polymorphisms (SNPs) of CYP2C9, CYP4F2, VKORC1 1173 and VKORC1-1639 influence warfarin maintenance dosage. We aimed to determine the impact of SNPs of these genes on mean daily warfarin dosage (MDWD) in Han-Chinese patients.Strict literature inclusion criteria were established, and literature searching was performed on PubMed, Embase and Cochrane Library for English articles and CNKI, CBM and Wanfang database for Chinese articles before September 2, 2014. Revman 5.3 was used to analyze the relationship between gene SNPs and MDWD in Han-Chinese subjects.We included 33 studies researching the impact of gene SNPs on MDWD in Han-Chinese subjects. CYP2C9 *3/*3, *1/*3 and *3 carriers needed a 72% (95% confidence interval [CI]: 62.0%-81.0%), 28% (22.0%-33.0%) and 26% (21.0%-32.0%) lower MDWD, respectively, than CYP2C9 *1/*1 carriers. CYP4F2 TT, CT and T carriers required a 18% (7.0%-30.0%), 7% (7.0%-7.0%) and 11% (7.0%-14.0%) higher MDWD, respectively, than CYP4F2 CC carriers. VKORC1 1173 CC, CT and C carriers required a 98% (78.0%-118.0%), 49% (37.0%-62.0%) and 56% (44.0%-67.0%) higher MDWD, respectively, than VKORC1 1173 TT carriers. VKORC1-1639 GG, GA and G carriers needed a 101% (53.0%-149.0%), 40% (36.0%-45.0%) and 38% (35.0%-42.0%) higher MDWD, respectively, than VKORC1-1639 AA carriers.This meta-analysis is the first to report the relationship between genotypes and MDWD among Han-Chinese patients. The results showed that SNPs of CYP2C9, CYP4F2, VKORC1 1173 and VKORC1-1639 significantly influenced the MDWD in Han-Chinese patients.
| S-EPMC5006145 | biostudies-other
Project description:Lung adenocarcinoma is a multifactorial disease. MicroRNA (miRNA) expression profiles are extensively used for discovering potential theranostic biomarkers of lung cancer. This work proposes an optimized support vector regression (SVR) method called SVR-LUAD to simultaneously identify a set of miRNAs referred to the miRNA signature for estimating the survival time of lung adenocarcinoma patients using their miRNA expression profiles. SVR-LUAD uses an inheritable bi-objective combinatorial genetic algorithm to identify a small set of informative miRNAs cooperating with SVR by maximizing estimation accuracy. SVR-LUAD identified 18 out of 332 miRNAs using 10-fold cross-validation and achieved a correlation coefficient of 0.88?±?0.01 and mean absolute error of 0.56?±?0.03 year between real and estimated survival time. SVR-LUAD performs well compared to some well-recognized regression methods. The miRNA signature consists of the 18 miRNAs which strongly correlates with lung adenocarcinoma: hsa-let-7f-1, hsa-miR-16-1, hsa-miR-152, hsa-miR-217, hsa-miR-18a, hsa-miR-193b, hsa-miR-3136, hsa-let-7g, hsa-miR-155, hsa-miR-3199-1, hsa-miR-219-2, hsa-miR-1254, hsa-miR-1291, hsa-miR-192, hsa-miR-3653, hsa-miR-3934, hsa-miR-342, and hsa-miR-141. Gene ontology annotation and pathway analysis of the miRNA signature revealed its biological significance in cancer and cellular pathways. This miRNA signature could aid in the development of novel therapeutic approaches to the treatment of lung adenocarcinoma.
| S-EPMC5548864 | biostudies-other
Project description:We investigated plasma microRNA (miRNA) profiles associated with variation of hyperglycemia, measured as hemoglobin A1c (HbA1c), in two panels of patients with type 1 diabetes (T1D). Using the HTG Molecular Diagnostics EdgeSeq platform, 2,083 miRNAs were measured in plasma from 71 patients included in a screening panel. Quantitative real-time PCR was used to measure the candidate miRNAs in plasma from 95 patients included in an independent replication panel. We found 10 miRNAs replicated in both panels and 4 with high statistical significance. The strongest positive correlations with HbA1c were found with miR-125b-5p (rs = 0.40, P = 6.0 × 10-5) and miR-365a-3p (rs = 0.35, P = 5.9 × 10-4). The strongest negative correlations were found with miR-5190 (rs = -0.30, P = 0.003) and miR-770-5p (rs = -0.27, P = 0.008). Pathway analysis revealed that 50 Kyoto Encyclopedia of Genes and Genomes pathways were significantly enriched by genes targeted by these four miRNAs. The axon guidance signaling pathway was enriched (P < 1 × 10-7) by genes targeted by all four miRNAs. In addition, three other pathways (Rap1 signaling, focal adhesion, and neurotrophin signaling) were also significantly enriched but with genes targeted by only by three of the identified miRNAs. In conclusion, our study identified four circulating miRNAs that were influenced by variation in hyperglycemia. Dysregulation of these miRNAs, which are associated with hyperglycemia in patients with T1D, may contribute to the development of diabetes complications. However, there are multitudes of possible mechanisms/pathways through which dysregulation of these miRNAs may impact risk of diabetes complications.
| S-EPMC5910001 | biostudies-literature