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https://www.readbyqxmd.com/read/28419892/plasma-apolipoproteins-and-physical-and-cognitive-health-in-very-old-individuals
#1
Julia Muenchhoff, Fei Song, Anne Poljak, John D Crawford, Karen A Mather, Nicole A Kochan, Zixuan Yang, Julian N Trollor, Simone Reppermund, Kate Maston, Adam Theobald, Susanne Kirchner-Adelhardt, John B Kwok, Robyn L Richmond, Mark McEvoy, John Attia, Peter W Schofield, Henry Brodaty, Perminder S Sachdev
Apolipoproteins play a crucial role in lipid metabolism with implications in cardiovascular disease, obesity, diabetes, Alzheimer's disease, and longevity. We quantified 7 apolipoproteins in plasma in 1067 individuals aged 56-105 using immunoassays and explored relationships with APOE polymorphism ε2/3/4, vascular health, frailty, and cognition. ApoA1, ApoA2, ApoB, ApoC3, ApoE, ApoH, and ApoJ decreased from mid-life, although ApoE and ApoJ had U-shaped trends. Centenarians had the highest ApoE levels and the lowest frequency of APOE ε4 allele relative to younger groups...
March 1, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28406212/human-knockouts-and-phenotypic-analysis-in-a-cohort-with-a-high-rate-of-consanguinity
#2
Danish Saleheen, Pradeep Natarajan, Irina M Armean, Wei Zhao, Asif Rasheed, Sumeet A Khetarpal, Hong-Hee Won, Konrad J Karczewski, Anne H O'Donnell-Luria, Kaitlin E Samocha, Benjamin Weisburd, Namrata Gupta, Mozzam Zaidi, Maria Samuel, Atif Imran, Shahid Abbas, Faisal Majeed, Madiha Ishaq, Saba Akhtar, Kevin Trindade, Megan Mucksavage, Nadeem Qamar, Khan Shah Zaman, Zia Yaqoob, Tahir Saghir, Syed Nadeem Hasan Rizvi, Anis Memon, Nadeem Hayyat Mallick, Mohammad Ishaq, Syed Zahed Rasheed, Fazal-Ur-Rehman Memon, Khalid Mahmood, Naveeduddin Ahmed, Ron Do, Ronald M Krauss, Daniel G MacArthur, Stacey Gabriel, Eric S Lander, Mark J Daly, Philippe Frossard, John Danesh, Daniel J Rader, Sekar Kathiresan
A major goal of biomedicine is to understand the function of every gene in the human genome. Loss-of-function mutations can disrupt both copies of a given gene in humans and phenotypic analysis of such 'human knockouts' can provide insight into gene function. Consanguineous unions are more likely to result in offspring carrying homozygous loss-of-function mutations. In Pakistan, consanguinity rates are notably high. Here we sequence the protein-coding regions of 10,503 adult participants in the Pakistan Risk of Myocardial Infarction Study (PROMIS), designed to understand the determinants of cardiometabolic diseases in individuals from South Asia...
April 12, 2017: Nature
https://www.readbyqxmd.com/read/28395986/a-decade-of-progress-on-the-genetic-basis-of-coronary-artery-disease-practical-insights-for-the-internist
#3
REVIEW
Domenico Girelli, Chiara Piubelli, Nicola Martinelli, Roberto Corrocher, Oliviero Olivieri
Clinicians are well aware of the importance of a positive family history for coronary artery disease (CAD). Nonetheless, elucidation of the genetic basis of CAD has long proven difficult. The scenario changed in the last decade through the application of modern genomic technologies, like genome-wide association studies (GWAS) and next generation sequencing (NGS). GWAS have discovered over 60 common variants highly associated with CAD. For predictive purposes, such variants have been used to build up Genetic Risk Scores (GRSs), but their incorporation into classical prediction models does not appear substantially outperform the simple addition of family history...
April 7, 2017: European Journal of Internal Medicine
https://www.readbyqxmd.com/read/28336922/novel-and-traditional-lipid-related-biomarkers-and-their-combinations-in-predicting-coronary-severity
#4
Sha Li, Yuan-Lin Guo, Xi Zhao, Yan Zhang, Cheng-Gang Zhu, Na-Qiong Wu, Rui-Xia Xu, Ping Qing, Ying Gao, Xiao-Lin Li, Jing Sun, Geng Liu, Qian Dong, Jian-Jun Li
We investigated simultaneously traditional and novel lipid indices, alone or in combination, in predicting coronary severity assessed by Gensini score (GS) in 1605 non-lipid-lowering-drug-treated patients undergoing coronary angiography. Firstly, levels of triglycerides (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), non high density lipoprotein cholesterol (non-HDL-C), apolipoprotein (apo) B, lipoprotein (a) [Lp(a)], proprotein convertase subtilisin/kexin type 9 (PCSK9), apoC3, small dense LDL (sdLDL) and large HDL were increased, while HDL-C and apoA1 levels were decreased as GS status (all p for trend <0...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28255847/n-3-benzoylphenyl-1h-indole-2-carboxamide-decreases-triglyceride-levels-by-downregulation-of-apoc3-gene-expression-in-acute-hyperlipidemic-rat-model
#5
Lama Hamadneh, Luay Al-Essa, Suhair Hikmat, Tariq Al-Qirim, Ghassan Abu Sheikha, Yusuf Al-Hiari, Nisrin Azmy, Ghassan Shattat
Hyperlipidemia is a known cause of coronary vascular diseases, which is a major cause of death in many parts of the world. Targeting several pathways that lead to increase in lipid profiles is of great potential to control diseases. 1H-indole-2-carboxamide derivatives were tested for their hypolipidemic activity at the molecular level in comparison with bezafibrate. The gene expression profiles of lipoprotein signaling and cholesterol metabolism and fatty acid metabolism PCR arrays were determined in rats with acute hyperlipidemia induced by Triton WR1339...
March 2, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28188435/marked-increase-in-urinary-excretion-of-apolipoproteins-in-children-with-nephrolithiasis-associated-with-hypercalciuria
#6
Larisa Kovacevic, Hong Lu, Joseph A Caruso, Tuhina Govil-Dalela, Ronald Thomas, Yegappan Lakshmanan
BACKGROUND: Using a proteomic approach, we aimed to identify and compare the urinary excretion of proteins involved in lipid transport and metabolism in children with kidney stones and hypercalciuria (CAL), hypocitraturia (CIT), and normal metabolic work-up (NM), and in healthy controls (HCs). Additionally, we aimed to confirm these results using ELISA, and to examine the relationship between the urinary excretion of selected proteins with demographic, dietary, blood, and urinary parameters...
February 10, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28139241/a-population-based-study-on-congenital-disorders-of-protein-n-and-combined-with-o-glycosylation-experience-in-clinical-and-genetic-diagnosis
#7
Celia Pérez-Cerdá, Ma Luisa Girós, Mercedes Serrano, M Jesús Ecay, Laura Gort, Belén Pérez Dueñas, Celia Medrano, Alfredo García-Alix, Rafael Artuch, Paz Briones, Belén Pérez
OBJECTIVE: To describe the clinical, biochemical, and genetic features of patients with congenital disorders of glycosylation (CDG) identified in Spain during the last 20 years. STUDY DESIGN: Patients were selected among those presenting with multisystem disease of unknown etiology. The isoforms of transferrin and of ApoC3 and dolichols were analyzed in serum; phosphomannomutase and mannosephosphate isomerase activities were measured in fibroblasts. Conventional or massive parallel sequencing (customized panel or Illumina Clinical-Exome Sequencing TruSight One Gene Panel) was used to identify genes and mutations...
January 27, 2017: Journal of Pediatrics
https://www.readbyqxmd.com/read/28115523/apoc3-protein-is-not-a-predisposing-factor-for-fat-induced-nonalcoholic-fatty-liver-disease-in-mice
#8
Xiaoyun Cheng, Jun Yamauchi, Sojin Lee, Ting Zhang, Zhenwei Gong, Radhika Muzumdar, Shen Qu, H Henry Dong
Nonalcoholic fatty liver disease (NAFLD), characterized by excessive fat accumulation in liver, is prevalent in obesity. Genetic factors that link obesity to NAFLD remain obscure. Apolipoprotein C3 (APOC3) is a lipid-binding protein with a pivotal role in triglyceride metabolism. Humans with APOC3 gain-of-function mutations and mice with APOC3 overproduction are associated with hypertriglyceridemia. Nonetheless, it remains controversial whether APOC3 is culpable for diet-induced NAFLD. To address this fundamental issue, we fed APOC3-transgenic and wild-type littermates a high fructose diet or high fat diet, followed by determination of the effect of APOC3 on hepatic lipid metabolism and inflammation and the progression of NAFLD...
March 3, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27843478/serum-protein-kng1-apoc3-and-pon1-as-potential-biomarkers-for-yin-deficiency-heat-syndrome
#9
Changming Liu, Liangen Mao, Zepeng Ping, Tingting Jiang, Chong Wang, Zhongliang Chen, Zhongjie Li, Jicheng Li
Yin-deficiency-heat (YDH) syndrome is a concept in Traditional Chinese Medicine (TCM) for describing subhealth status. However, there are few efficient diagnostic methods available for confirming YDH syndrome. To explore the novel method for diagnosing YDH syndrome, we applied iTRAQ to observe the serum protein profiles in YDH syndrome rats and confirmed protein levels by ELISA. A total of 92 differentially expressed proteins (63 upregulated proteins and 29 downregulated proteins), which were mainly involved in complement and coagulation cascades and glucose metabolism pathway, were identified by the proteomic experiments...
2016: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/27794214/lack-of-evidence-for-a-liver-or-intestinal-mirna-regulation-involved-in-the-hypertriglyceridemic-effect-of-apoc3-3-utr-variant-ssti
#10
Marine Dancer, Cyrielle Caussy, Mathilde Di Filippo, Philippe Moulin, Christophe Marçais, Sybil Charrière
BACKGROUND AND AIMS: APOC3 is a major regulator of triglycerides metabolism. Several APOC3 variants are associated with hypertriglyceridemia (HTG). Our aim was to establish the potential regulation of APOC3 3'UTR variants associated with HTG by liver or intestinal miRNAs. METHODS: We sequenced APOC3 3'UTR in 100 type 2 diabetic (TD2) patients with severe HTG (TG > 15 mmol/L) (HTG group) compared to 100 normotriglyceridemic patients (NTG group). We performed in silico studies to identify potential loss of miRNA binding induced by APOC3 3'UTR variants...
December 2016: Atherosclerosis
https://www.readbyqxmd.com/read/27794205/achieving-efficient-digestion-faster-with-flash-digest-potential-alternative-to-multi-step-detergent-assisted-in-solution-digestion-in-quantitative-proteomics-experiments
#11
Vinit Shah, Michael E Lassman, Ying Chen, Haihong Zhou, Omar F Laterza
RATIONALE: In quantitative analysis of protein biomarkers and therapeutic proteins by liquid chromatography/mass spectrometry (LC/MS), it is a preferred and well-established approach to digest with proteolytic enzymes to produce smaller peptide fragments which are more suitable for LC/MS analysis than the intact protein. In-solution digestion is one widely used method for protein digestion. Proteolytically resistant proteins often require digestion times that extend beyond normal working hours and prohibit same day analysis...
January 30, 2017: Rapid Communications in Mass Spectrometry: RCM
https://www.readbyqxmd.com/read/27766009/cardiac-manifestations-of-congenital-generalized-lipodystrophy
#12
Vani P Sanon, Yehuda Handelsman, Son V Pham, Robert Chilton
IN BRIEF Congenital lipodystrophy is a rare genetic disorder characterized by a near-complete absence of fat cells, hypoleptinemia leading to a voracious appetite, and marked insulin resistance. This article focuses on the known cardiovascular manifestations of patients with congenital lipodystrophy, including cardiomyopathy, cardiac arrhythmias, and accelerated atherosclerosis arising from a markedly deranged metabolic milieu. Future research that targets leptin deficiency (metreleptin) and apoC3 mRNA (antisense oligonucleotide) could open a window for potential pharmacological treatment of this challenging disorder...
October 2016: Clinical Diabetes: a Publication of the American Diabetes Association
https://www.readbyqxmd.com/read/27739219/using-human-genetics-to-discover-new-therapeutic-targets-for-plasma-lipids
#13
J C Cohen
Genetic variation arises through multiple different alleles that vary in frequency and severity of effect. Mutations that give rise to Mendelian disorders, such as the LDL receptor (LDLR) mutations that result in familial hypercholesterolaemia, are efficiently winnowed from the population by purifying selection and are almost inevitably rare. Conversely, alleles that are common in the population (such that homozygotes for the minor allele are present even in modest sample sizes) typically have very modest phenotypic effects...
October 14, 2016: Journal of Internal Medicine
https://www.readbyqxmd.com/read/27713142/novel-circulating-lipid-measurements-for-current-dyslipidemias-in-non-treated-patients-undergoing-coronary-angiography-pcsk9-apoc3-and-sdldl-c
#14
Sha Li, Xi Zhao, Yan Zhang, Cheng-Gang Zhu, Yuan-Lin Guo, Na-Qiong Wu, Rui-Xia Xu, Ping Qing, Ying Gao, Jing Sun, Geng Liu, Qian Dong, Jian-Jun Li
Plasma levels of proprotein convertase subtilisin/kexin type 9 (PCSK9), apolipoprotein C-III (apoC3) and small dense low density lipoprotein cholesterol (sdLDL-C), have been recently recognized as circulating atherosclerosis-related lipid measurements. We aimed to elucidate their associations with current dyslipidemias, and identify their levels at increased risk to dyslipidemia. A total of 1,605 consecutive, non-treated patients undergoing diagnostic/interventional coronary angiography were examined. Plasma PCSK9 and apoC3 levels were determined using a validated ELISA assay, and sdLDL-C was measured by the Lipoprint LDL System...
February 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/27690381/association-of-apolipoprotein-c3-genetic-polymorphisms-with-the-risk-of-ischemic-stroke-in-the-northern-chinese-han-population
#15
Yanzhe Wang, Xiaoyu Yin, Lei Li, Shumin Deng, Zhiyi He
The apolipoprotein C3 (APOC3) gene, which is a member of the APOA1/C3/A4/A5 gene cluster, plays a crucial role in lipid metabolism. Dyslipidemia is an important risk factor for ischemic stroke. In the present study, we performed a hospital-based case-control study of 895 ischemic stroke patients and 883 control subjects to examine the effects of four APOC3 single nucleotide polymorphisms (SNPs) (rs2854116, rs2854117, rs4520 and rs5128) on the risk of ischemic stroke in a northern Chinese Han population. The SNaPshot Multiplex sequencing assay was used for SNP genotyping, and the potential association of genotype distributions and allele frequencies with ischemic stroke was analyzed statistically...
2016: PloS One
https://www.readbyqxmd.com/read/27665711/the-rna-binding-protein-vigilin-regulates-vldl-secretion-through-modulation-of-apob-mrna-translation
#16
Mehrpouya B Mobin, Stefanie Gerstberger, Daniel Teupser, Benedetta Campana, Klaus Charisse, Markus H Heim, Muthiah Manoharan, Thomas Tuschl, Markus Stoffel
The liver is essential for the synthesis of plasma proteins and integration of lipid metabolism. While the role of transcriptional networks in these processes is increasingly understood, less is known about post-transcriptional control of gene expression by RNA-binding proteins (RBPs). Here, we show that the RBP vigilin is upregulated in livers of obese mice and in patients with fatty liver disease. By using in vivo, biochemical and genomic approaches, we demonstrate that vigilin controls very-low-density lipoprotein (VLDL) secretion through the modulation of apolipoproteinB/Apob mRNA translation...
September 26, 2016: Nature Communications
https://www.readbyqxmd.com/read/27648443/transcriptome-analysis-of-hepg2-cells-expressing-orf3-from-swine-hepatitis-e-virus-to-determine-the-effects-of-orf3-on-host-cells
#17
Kailian Xu, Shiyu Guo, Tianjing Zhao, Huapei Zhu, Hanwei Jiao, Qiaoyun Shi, Feng Pang, Yaying Li, Guohua Li, Dongmei Peng, Xin Nie, Ying Cheng, Kebang Wu, Li Du, Ke Cui, Wenguang Zhang, Fengyang Wang
Hepatitis E virus- (HEV-) mediated hepatitis has become a global public health problem. An important regulatory protein of HEV, ORF3, influences multiple signal pathways in host cells. In this study, to investigate the function of ORF3 from the swine form of HEV (SHEV), high-throughput RNA-Seq-based screening was performed to identify the differentially expressed genes in ORF3-expressing HepG2 cells. The results were validated with quantitative real-time PCR and gene ontology was employed to assign differentially expressed genes to functional categories...
2016: BioMed Research International
https://www.readbyqxmd.com/read/27624799/an-apoc3-3-utr-variant-associated-with-plasma-triglycerides-levels-and-coronary-heart-disease-by-creating-a-functional-mir-4271-binding-site
#18
Sen-Lin Hu, Guang-Lin Cui, Jin Huang, Jian-Gang Jiang, Dao-Wen Wang
Apolipoprotein C-III (APOC3) is a key regulator of plasma triglycerides levels. Increasing evidence has shown that loss-of-function mutations in APOC3 is associated with reduction in plasma triglycerides levels and will confer a benefit in patients at high risk for cardiovascular disease. However, these favorable mutations were extremely distribution discrepant among different ethnics. In this study, the APOC3 gene was resequenced and we identified a common variant which located in the microRNA-binding site in APOC3 and would affect its expression and the risk of coronary heart disease (CHD)...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27619170/apoc3-induces-endothelial-dysfunction-through-tnf-%C3%AE-and-jam-1
#19
Yun Tao, Yisong Xiong, Huimin Wang, Shaopeng Chu, Renqian Zhong, Jianxin Wang, Guihua Wang, Xiumei Ren, Juan Yu
BACKGROUND: The fatality rate for cardiovascular disease (CVD) has increased in recent years and higher levels of triglyceride have been shown to be an independent risk factor for atherosclerotic CVD. Dysfunction of endothelial cells (ECs) is also a key factor of CVD. APOC3 is an important molecule in lipid metabolism that is closely associated with hyperlipidemia and an increased risk of developing CVD. But the direct effects of APOC3 on ECs were still unknown. This study was aimed at determining the effects of APOC3 on inflammation, chemotaxis and exudation in ECs...
September 13, 2016: Lipids in Health and Disease
https://www.readbyqxmd.com/read/27578127/phenotypic-variability-in-4-homozygous-familial-hypercholesterolemia-siblings-compound-heterozygous-for-ldlr-mutations
#20
Claudio Rabacchi, Federico Bigazzi, Mariarita Puntoni, Francesco Sbrana, Tiziana Sampietro, Patrizia Tarugi, Stefano Bertolini, Sebastiano Calandra
BACKGROUND: Homozygous familial hypercholesterolemia is a rare clinical phenotype with a variable expression, which is characterized by extremely elevated plasma low-density lipoprotein (LDL), tendon and skin xanthomas, and a progressive atherosclerosis. In 95% of patients, homozygous familial hypercholesterolemia is due to mutations in low-density lipoprotein receptor (LDLR) gene, which abolish (receptor-negative) or greatly reduce (receptor-defective) LDLR function. OBJECTIVE: The objective of the study was the molecular and phenotypic characterization of 4 siblings with severe hypercholesterolemia...
July 2016: Journal of Clinical Lipidology
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