Use of a Panel of Congenic Strains to Evaluate Differentially Expressed Genes as Candidate Genes for Blood Pressure Quantitative Trait Loci.

Cha, Jin Soon; Liu, Jun; Qi, Nanshan; Ross, Anna Laura; Lee, Si Y.; George, Tiji

doi:10.1291/hypres.26.75

Cited by 30 publications

(5 citation statements)

References 39 publications

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“…Dahl salt-sensitive rats are the most popular animal model for investigations of the role of miRNAs in SSH [25] ; however, the results of these investigations may not be applicable to humans, due to species-specific differences. The miRNA panel that we constructed was able to distinguish SSH from SRH groups precisely and accurately.…”

Section: Discussionmentioning

confidence: 99%

micro-RNA screening and prediction model construction for diagnosis of salt-sensitive essential hypertension

Han

Liu

et al. 2017

Medicine

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Commonly used tests for diagnosis of salt-sensitive hypertension (SSH) are complex and time-consuming, so new methods are required. Many studies have demonstrated roles for miRNAs in hypertension; however, the diagnostic value of miRNAs has yet to be determined for human SSH. In this study, we examined miRNA expression profiles by initial high-throughput miRNA sequencing of samples from patients with salt-sensitive and salt-resistant hypertension (SSH and SRH, respectively; n = 6, both groups), followed by validation by quantitative real-time polymerase chain reaction (qRT-PCR) in a larger cohort (n = 91). We also evaluated differences in baseline characteristics (e.g., age, sex, body mass index, consumption of specific foods) between the SSH and SRH groups. Of 36 miRNAs identified as differentially expressed between SSH and SRH groups by RNA-Seq, 8 were analyzed by qRT-PCR. There were significant differences in the expression levels of hsa-miR-361-5p and hsa-miR-362-5p between the 2 groups (P = .023 and.049, respectively). In addition, there were significant differences in sauce and poultry consumption between the 2 groups (P = .004 and.001, respectively). The areas under the curve (AUC) determined by receptor operating characteristic (ROC) analysis for hsa-miR-361–5p and all 8 miRNAs were 0.793 (95% CI, 0.698–0.888; sensitivity = 73.9%, specificity = 74.4%; P < .001) and 0.836 (95% CI, 0.749–0.922; sensitivity = 80.4%, specificity = 81.4%; P < .001), respectively, when sauce and poultry consumption were included in the models. Assay feasibility and economic considerations make hsa-miR-361-5p combined with the dietary factors the preferred markers for diagnosis of SSH.

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Section: Discussionmentioning

confidence: 99%

micro-RNA screening and prediction model construction for diagnosis of salt-sensitive essential hypertension

Han

Liu

et al. 2017

Medicine

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“…The candidate gene approach has led to notable success in demonstrating reproduction-related genetic markers or major genes, such as ES R, the erythopoietin receptor ( EPOR ), the prolactin receptor ( PRLR ), FSH-β and RBP4 [1,5,41-43]. Differentially expressed transcripts also can be evaluated as potential candidates if they meet the following criteria: the chromosomal location to a region containing a QTL, the importance of the tissue of interest in regulating the expression of the specific quantitative trait, and the critical developing stage responsible for the differences in the specific quantitative trait [44]. …”

Section: Discussionmentioning

confidence: 99%

Microarray profiling for differential gene expression in PMSG-hCG stimulated preovulatory ovarian follicles of Chinese Taihu and Large White sows

et al. 2011

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BackgroundThe Chinese Taihu is one of the most prolific pig breeds in the world, which farrows at least five more piglets per litter than Western pig breeds partly due to a greater ovulation rate. Variation of ovulation rate maybe associated with the differences in the transcriptome of Chinese Taihu and Large White ovaries. In order to understand the molecular basis of the greater ovulation rate of Chinese Taihu sows, expression profiling experiments were conducted to identify differentially expressed genes in ovarian follicles at the preovulatory stage of a PMSG-hCG stimulated estrous cycle from 3 Chinese Taihu and 3 Large White cycling sows by using the Affymetrix Porcine Genechip™.ResultsOne hundred and thirty-three differentially expressed genes were identified between Chinese Taihu and Large White sows by using Affymetrix porcine GeneChip (p ≤ 0.05, Fold change ≥ 2 or ≤ 0.5). Gene Ontology (GO) analysis revealed that these genes belonged to the class of genes that participated in regulation of cellular process, regulation of biological process, biological regulation, developmental process, cell communication and signal transduction and so on. Significant differential expression of 6 genes including WNT10B and DKK2 in the WNT signaling pathway was detected. Real-time RT-PCR confirmed the expression pattern in seven of eight selected genes. A search of chromosomal location revealed that 92 differentially expressed transcripts located to the intervals of quantitative trait loci (QTLs) for reproduction traits. Furthermore, SNPs of two differentially expressed genes- BAX and BMPR1B were showed to be associated with litter size traits in Large White pigs and Chinese DIV line pigs (p ≤ 0.1 or p ≤ 0.05).ConclusionsOur study detected many genes that showed differential expression between ovary follicles of two divergent breeds of pigs. Genes involved with regulation of cellular process, regulation of biological process, in addition to several genes not previously associated with ovarian physiology or with unknown function, were differentially expressed between two breeds. The suggestive or significant associations of BAX and BMPR1B gene with litter size indicated these genetic markers had the potentials to be used in pig industry after further validation of their genetic effects. Taken together, this study reveals many potential avenues of investigation for seeking new insights into ovarian physiology and the genetic control of reproduction.

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“…Inhibition of hydroxyacid oxidase 2 (HAO2) in the reduced kidney model led to reduced glutamate, glycine, and serine reabsorption suggesting a possible role for HAO2 in the hypertensive side effect following CETP inhibitor treatment based on the association of amino acid reabsorption with vasodilation and hypertension (see Table 1). HAO2 is highly expressed in human kidney [28] and was identified as a candidate quantitative trait locus for blood pressure in rat kidney in a study comparing normal to hypertensive rats [29].…”

Section: Resultsmentioning

confidence: 99%

Drug Off-Target Effects Predicted Using Structural Analysis in the Context of a Metabolic Network Model

et al. 2010

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Recent advances in structural bioinformatics have enabled the prediction of protein-drug off-targets based on their ligand binding sites. Concurrent developments in systems biology allow for prediction of the functional effects of system perturbations using large-scale network models. Integration of these two capabilities provides a framework for evaluating metabolic drug response phenotypes in silico. This combined approach was applied to investigate the hypertensive side effect of the cholesteryl ester transfer protein inhibitor torcetrapib in the context of human renal function. A metabolic kidney model was generated in which to simulate drug treatment. Causal drug off-targets were predicted that have previously been observed to impact renal function in gene-deficient patients and may play a role in the adverse side effects observed in clinical trials. Genetic risk factors for drug treatment were also predicted that correspond to both characterized and unknown renal metabolic disorders as well as cryptic genetic deficiencies that are not expected to exhibit a renal disorder phenotype except under drug treatment. This study represents a novel integration of structural and systems biology and a first step towards computational systems medicine. The methodology introduced herein has important implications for drug development and personalized medicine.

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Use of a Panel of Congenic Strains to Evaluate Differentially Expressed Genes as Candidate Genes for Blood Pressure Quantitative Trait Loci.

Cited by 30 publications

References 39 publications

micro-RNA screening and prediction model construction for diagnosis of salt-sensitive essential hypertension

micro-RNA screening and prediction model construction for diagnosis of salt-sensitive essential hypertension

Microarray profiling for differential gene expression in PMSG-hCG stimulated preovulatory ovarian follicles of Chinese Taihu and Large White sows

Drug Off-Target Effects Predicted Using Structural Analysis in the Context of a Metabolic Network Model

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