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APOE Gene

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https://www.readbyqxmd.com/read/28334117/a-generalized-association-test-based-on-u-statistics
#1
Changshuai Wei, Qing Lu
Motivation: Second generation sequencing technologies are being increasingly used for genetic association studies, where the main research interest is to identify sets of genetic variants that contribute to various phenotypes. The phenotype can be univariate disease status, multivariate responses and even high-dimensional outcomes. Considering the genotype and phenotype as two complex objects, this also poses a general statistical problem of testing association between complex objects...
February 17, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28332615/integrative-variants-haplotypes-and-diplotypes-of-the-capn3-and-frmd5-genes-and-several-environmental-exposures-associate-with-serum-lipid-variables
#2
Tao Guo, Rui-Xing Yin, Ling Pan, Shuo Yang, Liu Miao, Feng Huang
To determine whether the integrative variants, haplotypes and diplotypes of the calpain 3 (CAPN3) and the FERM domain containing 5 genes (FRMD5) and several environmental exposures are associated with an implication in lipid homeostasis, which are associated with cardiovascular risk. Genotyping of the CAPN3 rs4344713 and FRMD5 rs524908 was performed by Sanger sequencing in 1,640 subjects (Jing, 819 and Han, 821). Multivariate analyses of covariance models that adjusted by age, gender, body mass index (BMI), blood pressure and lifestyle (smoking and drinking), were constructed using variants, haplotypes and diplotypes of the CAPN3 rs4344713 and FRMD5 rs524908 as predictors and changes in lipid variables...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28330871/human-mitochondrial-cytochrome-c-oxidase-assembly-factor-cox18-acts-transiently-as-a-membrane-insertase-within-the-subunit-2-maturation-module
#3
Myriam Bourens, Antoni Barrientos
Defects in mitochondrial cytochrome c oxidase or respiratory chain complex IV (CIV) assembly are a frequent cause of human mitochondrial disorders. Specifically, mutations in four conserved assembly factors impinging the biogenesis of the mitochondrion-encoded catalytic core subunit 2 (COX2) result in myopathies. These factors afford stability of newly-synthesized COX2 (the dystonia-ataxia syndrome protein COX20), a protein with two transmembrane domains, and maturation of its copper center CuA (cardiomyopathy proteins SCO1, SCO2 and COA6)...
March 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28327386/smoking-dependent-effect-of-lpl-and-apo-ciii-genes-on-cad-risk-in-an-african-brazilian-population
#4
Edilene M Q Araújo, Caio C S Cerqueira, Laila Freitas-Santos, Claubert R Coutinho, Ana A L Barbosa, Sandra M B Sousa, Larissa O Guimarães, Lydia L S Korontai, Jamille S Oliveira, Karolline S Silva, Domingos L S Rios
No abstract text is available yet for this article.
December 2016: Atherosclerosis
https://www.readbyqxmd.com/read/28326151/chronic-porphyromonas-gingivalis-infection-accelerates-the-occurrence-of-age-related-granules-in-apoe-mice-brains
#5
Sim K Singhrao, Sasanka Chukkapalli, Sophie Poole, Irina Velsko, St John Crean, Lakshmyya Kesavalu
This study explored the origin of age-related granules in the apolipoprotein E gene knockout (ApoE(-/-)) B6 background mice brains following chronic gingival infection with Porphyromonas gingivalis for 24 weeks. Intracerebral localization of P. gingivalis was detected by fluorescence in situ hybridization (FISH) and its protease by immunohistochemistry. The age-related granules were observed by periodic acid-Schiff (PAS), silver impregnation, and immunostaining. FISH showed intracerebral dissemination of P...
2017: Journal of Oral Microbiology
https://www.readbyqxmd.com/read/28323831/genetic-assessment-of-age-associated-alzheimer-disease-risk-development-and-validation-of-a-polygenic-hazard-score
#6
Rahul S Desikan, Chun Chieh Fan, Yunpeng Wang, Andrew J Schork, Howard J Cabral, L Adrienne Cupples, Wesley K Thompson, Lilah Besser, Walter A Kukull, Dominic Holland, Chi-Hua Chen, James B Brewer, David S Karow, Karolina Kauppi, Aree Witoelar, Celeste M Karch, Luke W Bonham, Jennifer S Yokoyama, Howard J Rosen, Bruce L Miller, William P Dillon, David M Wilson, Christopher P Hess, Margaret Pericak-Vance, Jonathan L Haines, Lindsay A Farrer, Richard Mayeux, John Hardy, Alison M Goate, Bradley T Hyman, Gerard D Schellenberg, Linda K McEvoy, Ole A Andreassen, Anders M Dale
BACKGROUND: Identifying individuals at risk for developing Alzheimer disease (AD) is of utmost importance. Although genetic studies have identified AD-associated SNPs in APOE and other genes, genetic information has not been integrated into an epidemiological framework for risk prediction. METHODS AND FINDINGS: Using genotype data from 17,008 AD cases and 37,154 controls from the International Genomics of Alzheimer's Project (IGAP Stage 1), we identified AD-associated SNPs (at p < 10-5)...
March 2017: PLoS Medicine
https://www.readbyqxmd.com/read/28323660/impact-of-rare-variants-in-autosomal-dominant-hypercholesterolemia-causing-genes
#7
Sebastiano Calandra, Patrizia Tarugi, Stefano Bertolini
PURPOSE OF REVIEW: The systematic analysis of the major candidate genes in autosomal dominant hypercholesterolemia (ADH) and the use of next-generation sequencing (NGS) technology have made possible the discovery of several rare gene variants whose pathogenic effect in most cases remains poorly defined. RECENT FINDINGS: One major advance in the field has been the adoption of a set of international guidelines for the assignment of pathogenicity to low-density lipoprotein receptor (LDLR) gene variants based on the use of softwares, complemented with data available from literature and public databases...
March 18, 2017: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/28323160/effect-of-age-and-the-apoe-gene-on-metabolite-concentrations-in-the-posterior-cingulate-cortex
#8
Sana Suri, Uzay Emir, Charlotte J Stagg, Jamie Near, Ralf Mekle, Florian Schubert, E Zsoldos, Abda Mahmood, Archana Singh-Manoux, Mika Kivimäki, Klaus P Ebmeier, Clare E Mackay, Nicola Filippini
Proton magnetic resonance spectroscopy ((1)H-MRS) has provided valuable information about the neurochemical profile of Alzheimer's disease (AD). However, its clinical utility has been limited in part by the lack of consistent information on how metabolite concentrations vary in the normal aging brain and in carriers of apolipoprotein E (APOE) ε4, an established risk gene for AD. We quantified metabolites within an 8cm(3) voxel within the posterior cingulate cortex (PCC)/precuneus in 30 younger (20-40 years) and 151 cognitively healthy older individuals (60-85 years)...
March 16, 2017: NeuroImage
https://www.readbyqxmd.com/read/28322000/postprandial-triglyceride-rich-lipoproteins-promote-lipid-accumulation-and-apolipoprotein-b-48-receptor-transcriptional-activity-in-human-circulating-and-murine-bone-marrow-neutrophils-in-a-fatty-acid-dependent-manner
#9
Almudena Ortega-Gómez, Lourdes M Varela, Sergio Lopez, Sergio Montserrat de la Paz, Rosario Sanchez, Francisco J G Muriana, Beatriz Bermúdez, Rocío Abia
SCOPE: Postprandial triglyceride-rich lipoproteins (TRLs) promote atherosclerosis. Recent research points the bone marrow (BM) as a primary site in atherosclerosis. We elucidated how the acute administration of MUFAs, omega-3 PUFAs and saturated fatty acids (SFAs) affects human circulating and murine BM neutrophil lipid accumulation and functionality. METHODS AND RESULTS: Postprandial hypertriglyceridemia was induced in healthy subjects and Apoe-/- mice by the acute administration of dietary fats enriched in MUFAs, PUFAs or SFAs...
March 21, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28321820/apolipoprotein-e4-suppresses-neuronal-specific-gene-expression-in-maturing-neuronal-progenitor-cells-exposed-to-hiv
#10
Rebeca Geffin, Ricardo Martinez, Alicia de Las Pozas, Biju Issac, Micheline McCarthy
The apolipoprotein ε4 gene allele and the apolipoprotein E4 protein (ApoE4) are important host susceptibility factors linked to neurocognitive disorders associated with HIV infection or Alzheimer's disease. Our previous studies showed differential effects of the two most common human ApoE genotypes, APOE3/3 and APOE3/4, on gene expression by differentiating human neuroepithelial progenitor cells continuously exposed to HIV. To investigate the effects of ApoE3 versus ApoE4 isoforms specifically on maturing neurons, we adapted a human neuronal progenitor cell line, hNP1, with ApoE genotype APOE3/3...
March 20, 2017: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/28320530/single-cell-rna-sequence-analysis-of-mouse-glomerular-mesangial-cells-uncovers-mesangial-cell-essential-genes
#11
Yuqiu Lu, Yuting Ye, Qianqian Yang, Shaolin Shi
Mesangial cells are essential for the structure and function of glomeruli, but the mechanisms underlying these roles are not well understood. Here, we performed a single-cell RNA-sequence (RNA-seq) analysis of mouse mesangial cells using the Fluidigm C1 platform. We found that gene expression in individual mesangial cells was tremendously heterogeneous, with mean correlation coefficients of 0.20, and most mesangial genes were actually expressed in only a portion of mesangial cells and are therefore presumably dispensable...
March 17, 2017: Kidney International
https://www.readbyqxmd.com/read/28320416/effect-of-the-r92h-and-a379v-genotypes-of-platelet-activating-factor-acetylhydrolase-on-its-enzyme-activity-oxidative-stress-and-metabolic-profile-in-chinese-women-with-polycystic-ovary-syndrome
#12
Renjiao Zhang, Qi Song, Hongwei Liu, Huai Bai, Yujin Zhang, Qingqing Liu, Linbo Guan, Ping Fan
BACKGROUND: The G994T polymorphism in platelet-activating factor acetylhydrolase (PAF-AH) gene is associated with the risk of polycystic ovary syndrome (PCOS). The aim of this study was to investigate the relationship between R92H and A379V variants of the PAF-AH gene and the risk of PCOS and to evaluate the effects of the genotypes on PAF-AH activities and clinical, metabolic and oxidative stress indexes in Chinese women. METHODS: A total of 862 patients with PCOS based on the Rotterdam consensus criteria and 750 control women from a population of Chinese Han nationality in the Chengdu area were studied from 2006-2015...
March 20, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28319084/structural-and-mechanistic-insights-into-an-archaeal-dna-guided-argonaute-protein
#13
Sarah Willkomm, Christine A Oellig, Adrian Zander, Tobias Restle, Ronan Keegan, Dina Grohmann, Sabine Schneider
Argonaute (Ago) proteins in eukaryotes are known as key players in post-transcriptional gene silencing(1), while recent studies on prokaryotic Agos hint at their role in the protection against invading DNA(2,3). Here, we present crystal structures of the apo enzyme and a binary Ago-guide complex of the archaeal Methanocaldococcus jannaschii (Mj) Ago. Binding of a guide DNA leads to large structural rearrangements. This includes the structural transformation of a hinge region containing a switch helix, which has been shown for human Ago2 to be critical for the dynamic target search process(4-6)...
March 20, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28315324/nucleolin-protects-macrophages-from-oxldl-induced-foam-cell-formation-through-up-regulating-abca1-expression
#14
Yuanbin Li, Bimei Jiang, Pengfei Liang, Zhongyi Tong, Meidong Liu, Qinglan Lv, Yanjuan Liu, Xuanyou Liu, Yuting Tang, Xianzhong Xiao
Our recent studies have indicated that nucleolin, as a multifunctional RNA-binding protein, exerts protective effects in the myocardial cells and endothelial cells under the condition of oxidative stress. However, the function of nucleolin and its potential mechanism in macrophage-derived foam cell formation remain largely unexplored. ApoE-/- mice were fed with a high-fat diet (HFD) for 10-24 weeks. Protein expression was measured by western blotting or immunofluorescence, and gene expression at the mRNA level was detected by qRT-PCR...
March 14, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28299413/apolipoprotein-e-the-resilience-gene
#15
Lisa M James, Brian E Engdahl, Apostolos P Georgopoulos
The apolipoprotein E (apoE) gene has been implicated in various conditions, most notably Alzheimer's disease and coronary artery disease. A predisposing role of the apoE4 isoform and a protective role of apoE2 isoform in those diseases have been documented. Here we investigated the role of apoE in resilience to trauma. Three hundred and forty-three US veterans were genotyped for apoE and were assessed for their lifetime trauma exposure (trauma score, T) and severity of posttraumatic stress disorder symptoms (PCL)...
March 15, 2017: Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
https://www.readbyqxmd.com/read/28294061/the-association-of-mme-microrna-binding-site-polymorphism-with-risk-of-late-onset-alzheimer-s-disease-in-northern-han-chinese
#16
Chun-Xia Liu, Lin Tan, Fu-Rong Sun, Wei Zhang, Dan Miao, Meng-Shan Tan, Yu Wan, Chen-Chen Tan, Jin-Tai Yu, Lan Tan
Background Although amyloid β (Aβ) degradation has been normally implicated in the pathogenesis of late onset Alzheimer's disease (LOAD) through cellular biological studies, genetic studies linking Aβ degradation and LOAD are still not deeply investigated. Neprilysin (NEP), as one of the most crucial Aβ-degrading enzymes in AD, is the metalloendopeptidases which particularly participates in the monomeric Aβ species degradation. MicroRNAs (miRNAs) exert posttranscriptional dysregulation and their target sequence on the 3' untranslated regions (3'UTR) may be regulated by single nucleotide polymorphisms (SNPs)...
March 13, 2017: Current Neurovascular Research
https://www.readbyqxmd.com/read/28292897/inhibition-of-atherogenesis-by-the-cop9-signalosome-subunit-5-in-vivo
#17
Yaw Asare, Miriam Ommer, Florence A Azombo, Setareh Alampour-Rajabi, Marieke Sternkopf, Maryam Sanati, Marion J Gijbels, Corinna Schmitz, Dzmitry Sinitski, Pathricia V Tilstam, Hongqi Lue, André Gessner, Denise Lange, Johannes A Schmid, Christian Weber, Martin Dichgans, Joachim Jankowski, Ruggero Pardi, Menno P J de Winther, Heidi Noels, Jürgen Bernhagen
Constitutive photomorphogenesis 9 (COP9) signalosome 5 (CSN5), an isopeptidase that removes neural precursor cell-expressed, developmentally down-regulated 8 (NEDD8) moieties from cullins (thus termed "deNEDDylase") and a subunit of the cullin-RING E3 ligase-regulating COP9 signalosome complex, attenuates proinflammatory NF-κB signaling. We previously showed that CSN5 is up-regulated in human atherosclerotic arteries. Here, we investigated the role of CSN5 in atherogenesis in vivo by using mice with myeloid-specific Csn5 deletion...
March 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28291242/mining-outcome-relevant-brain-imaging-genetic-associations-via-three-way-sparse-canonical-correlation-analysis-in-alzheimer-s-disease
#18
Xiaoke Hao, Chanxiu Li, Lei Du, Xiaohui Yao, Jingwen Yan, Shannon L Risacher, Andrew J Saykin, Li Shen, Daoqiang Zhang
Neuroimaging genetics is an emerging field that aims to identify the associations between genetic variants (e.g., single nucleotide polymorphisms (SNPs)) and quantitative traits (QTs) such as brain imaging phenotypes. In recent studies, in order to detect complex multi-SNP-multi-QT associations, bi-multivariate techniques such as various structured sparse canonical correlation analysis (SCCA) algorithms have been proposed and used in imaging genetics studies. However, associations between genetic markers and imaging QTs identified by existing bi-multivariate methods may not be all disease specific...
March 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28291223/liver-specific-deletion-of-the-plpp3-gene-alters-plasma-lipid-composition-and-worsens-atherosclerosis-in-apoe-mice
#19
Marco Busnelli, Stefano Manzini, Mika Hilvo, Cinzia Parolini, Giulia S Ganzetti, Federica Dellera, Kim Ekroos, Minna Jänis, Diana Escalante-Alcalde, Cesare R Sirtori, Reijo Laaksonen, Giulia Chiesa
The PLPP3 gene encodes for a ubiquitous enzyme that dephosphorylates several lipid substrates. Genome-wide association studies identified PLPP3 as a gene that plays a role in coronary artery disease susceptibility. The aim of the study was to investigate the effect of Plpp3 deletion on atherosclerosis development in mice. Because the constitutive deletion of Plpp3 in mice is lethal, conditional Plpp3 hepatocyte-specific null mice were generated by crossing floxed Plpp3 mice with animals expressing Cre recombinase under control of the albumin promoter...
March 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28273782/active-liver-x-receptor-signaling-in-phagocytes-in-multiple-sclerosis-lesions
#20
Jo Mailleux, Tim Vanmierlo, Jeroen Fj Bogie, Elien Wouters, Dieter Lütjohann, Jerome Ja Hendriks, Jack van Horssen
OBJECTIVE: We sought to determine the liver X receptor (LXR) ligands present in human macrophages after myelin phagocytosis and whether LXRs are activated in multiple sclerosis (MS) lesions. METHODS: We used real-time quantitative polymerase chain reaction (PCR) and immunohistochemistry to determine expression of LXRs and their response genes in human phagocytes after myelin phagocytosis and in active MS lesions. We used gas chromatographic/mass spectrometric analysis to determine LXR-activating oxysterols and cholesterol precursors present and formed in myelin and myelin-incubated cells, respectively...
February 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
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