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https://www.readbyqxmd.com/read/29320745/the-foxo1-inducible-transcriptional-repressor-zfp125-causes-hepatic-steatosis-and-hypercholesterolemia
#1
Gustavo W Fernandes, Barbara M L C Bocco, Tatiana L Fonseca, Elizabeth A McAninch, Sungro Jo, Lattoya J Lartey, InSug O-Sullivan, Terry G Unterman, Nailliw Z Preite, Robin M Voigt, Christopher B Forsyth, Ali Keshavarzian, Richárd Sinkó, Allison B Goldfine, Mary E Patti, Miriam O Ribeiro, Balázs Gereben, Antonio C Bianco
Liver-specific disruption of the type 2 deiodinase gene (Alb-D2KO) results in resistance to both diet-induced obesity and liver steatosis in mice. Here, we report that this is explained by an ∼60% reduction in liver zinc-finger protein-125 (Zfp125) expression. Zfp125 is a Foxo1-inducible transcriptional repressor that causes lipid accumulation in the AML12 mouse hepatic cell line and liver steatosis in mice by reducing liver secretion of triglycerides and hepatocyte efflux of cholesterol. Zfp125 acts by repressing 18 genes involved in lipoprotein structure, lipid binding, and transport...
January 9, 2018: Cell Reports
https://www.readbyqxmd.com/read/29313574/a-study-of-genetic-markers-in-patients-of-rheumatoid-arthritis-and-their-co-relation-with-severity-of-the-disease
#2
Gauri Liyakat Ali, Suman Kapur, Sai Chinmayi, Qadir Fatima, Harshal Pise, Asim Khan, Ambreen Liyakat, V Jilova, Urvashi Dube
Introduction: Dyslipidemia has been reported to attribute to early death due to increased atherosclerosis leading to CVDs in patients with RA. Recent reports have suggested a role of adipocytokines in mediating joint damage rheumatoid arthritis (RA). RA has long been associated with increased cardiovascular risk as atherosclerosis is more prevalent in patients of RA than in the general population. Specific alleles of APOE gene have been reported to be associated with risk for atherosclerosis and LEP gene alleles have been associated with increased BMI...
September 2017: Journal of the Association of Physicians of India
https://www.readbyqxmd.com/read/29285134/sicyos-angulatus-ameliorates-atherosclerosis-through-downregulation-of-aortic-inflammatory-responses-in-apolipoprotein-e-deficient-mice
#3
Yong-Hoon Kim, Jung-Ran Noh, Jung Hwan Hwang, Kyoung-Shim Kim, Dong-Hee Choi, Jin-Pyo An, Won-Keun Oh, Chul-Ho Lee
Sicyos angulatus (SA), a summer annual vine originating from Northeastern USA, is a widely distributed noxious invasive plant. However, the clinical application of SA has not been investigated previously. The purpose of present study was to determine the effects of SA on atherosclerosis and its underlying mechanism. Atherosclerosis was induced by feeding apolipoprotein E-deficient (apoE-/-) mice with an atherogenic diet for 8 weeks. SA was administered daily by oral gavage during induction of atherosclerosis...
December 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29278888/healthy-versus-entorhinal-cortical-atrophy-identification-in-asymptomatic-apoe4-carriers-at-risk-for-alzheimer-s-disease
#4
Kyoko Konishi, Ridha Joober, Judes Poirier, Kathleen MacDonald, Mallar Chakravarty, Raihaan Patel, John Breitner, Véronique D Bohbot
Early detection of Alzheimer's disease (AD) has been challenging as current biomarkers are invasive and costly. Strong predictors of future AD diagnosis include lower volume of the hippocampus and entorhinal cortex, as well as the ɛ4 allele of the Apolipoprotein E gene (APOE) gene. Therefore, studying functions that are critically mediated by the hippocampus and entorhinal cortex, such as spatial memory, in APOE ɛ4 allele carriers, may be key to the identification of individuals at risk of AD, prior to the manifestation of cognitive impairments...
December 16, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29273831/synergism-between-apolipoprotein-e-%C3%A6-4-allele-and-paraoxonase-pon1-55-m-allele-is-associated-with-risk-of-systemic-lupus-erythematosus
#5
Maryam Tanhapour, Ali Miri, Asad Vaisi-Raygani, Fariborz Bahrehmand, Amir Kiani, Zohreh Rahimi, Tayebeh Pourmotabbed, Ebrahim Shakiba
Evidences indicate that abnormal lipid metabolism and lipid peroxidation can affect the progression of complications in systemic lupus erythematosus (SLE) patients. Apolipoprotein E (ApoE) and paraoxonase-1 (PON1) play important role in lipid metabolism and protection of lipid peroxidation. The polymorphisms of ApoE and paraoxonase (PON1) L55M (Met < Leu) allele genes lead to disorders in lipid metabolism and are related to atherosclerosis. This study is the first investigation to examine the possible association between ApoE and PON1-L55M polymorphisms and correlation with serum arylesterase (ARE) activities of PON, levels of malondialdehyde (MDA), neopterin, and lipid lipoprotein in SLE patients from Iranian western population...
December 22, 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/29258400/evaluation-of-apoe-genotype-and-ability-to-perform-activities-of-daily-living-following-aneurysmal-subarachnoid-hemorrhage
#6
Lacey Wright Heinsberg, Eleanor Turi, Dianxu Ren, Elizabeth Crago, Sheila Alexander, Ansley Grimes Stanfill, Yvette Perry Conley
Survivors of aneurysmal subarachnoid hemorrhage (aSAH) often experience unfavorable functional outcomes that result in a reduced ability to independently perform activities of daily living. The apolipoprotein E gene ( APOE) encodes for a protein known to facilitate lipid transport and aid in neuronal repair within the central nervous system and to moderate the inflammatory response, making functional variations in this gene likely candidate biomarkers to predict outcomes following aSAH. In the present work, we examined the relationship between APOE genotype and the ability to perform activities of daily living as measured by the Barthel Index (BI) score at 3 months ( n = 298) and 12 months ( n = 288) following aSAH...
January 1, 2017: Biological Research for Nursing
https://www.readbyqxmd.com/read/29246571/generation-and-characterization-of-human-induced-pluripotent-stem-cell-hipsc-lines-from-an-alzheimer-s-disease-asui003-a-and-non-demented-control-asui004-a-patient-homozygous-for-the-apolipoprotein-e4-apoe4-risk-variant
#7
Nicholas Brookhouser, Ping Zhang, Richard Caselli, Jean J Kim, David A Brafman
Although the majority of late-onset Alzheimer's disease (AD) patients are labeled sporadic, multiple genetic risk variants have been identified, the most powerful and prevalent of which is the e4 variant of the Apolipoprotein E (APOE) gene. Here, we generated human induced pluripotent stem cell (hiPSC) lines from the peripheral blood mononuclear cells (PBMCs) of a clinically diagnosed AD patient [ASUi003-A] and a non-demented control (NDC) patient [ASUi004-A] homozygous for the APOE4 risk allele. These hiPSCs maintained their original genotype, expressed pluripotency markers, exhibited a normal karyotype, and retained the ability to differentiate into cells representative of the three germ layers...
December 2017: Stem Cell Research
https://www.readbyqxmd.com/read/29221940/pioglitazone-attenuates-aging-related-disorders-in-aged-apolipoprotein-e-deficient-mice
#8
Dan Shen, Hao Li, Rui Zhou, Meng-Jie Liu, Hong Yu, Dong-Fang Wu
Pioglitazone (Piog) activates peroxisome proliferator activated receptor-γ (PPARγ) and is widely used in clinic for the treatment of diabetes mellitus. PPARγ in various tissues has the essential regulatory role of multiple metabolic function, suggest that PPARγ signaling may contribute to aging processes. However, little is known about the consequences of Piog on aging in aged animal models. We used apolipoprotein E deficient (apoE-/-) mice model to evaluate the effects of Piog on aging-related disorders...
December 5, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/29216449/apoe4-accelerates-early-seeding-of-amyloid-pathology
#9
Chia-Chen Liu, Na Zhao, Yuan Fu, Na Wang, Cynthia Linares, Chih-Wei Tsai, Guojun Bu
Accumulation and aggregation of amyloid-β (Aβ) in the brain is an initiating step in the pathogenesis of Alzheimer's disease (AD). The ε4 allele of apolipoprotein E (apoE) gene is the strongest genetic risk factor for late-onset AD. Although there is strong evidence showing that apoE4 enhances amyloid pathology, it is not clear what the critical stage(s) is during amyloid development in which apoE4 has the strongest impact. Using apoE inducible mouse models, we show that increased expression of astrocytic apoE4, but not apoE3, during the seeding stage of amyloid development enhanced amyloid deposition and neuritic dystrophy in amyloid model mice...
December 6, 2017: Neuron
https://www.readbyqxmd.com/read/29216448/age-dependent-effects-of-apoe-reduction-using-antisense-oligonucleotides-in-a-model-of-%C3%AE-amyloidosis
#10
Tien-Phat V Huynh, Fan Liao, Caroline M Francis, Grace O Robinson, Javier Remolina Serrano, Hong Jiang, Joseph Roh, Mary Beth Finn, Patrick M Sullivan, Thomas J Esparza, Floy R Stewart, Thomas E Mahan, Jason D Ulrich, Tracy Cole, David M Holtzman
The apolipoprotein E (APOE) gene is the strongest genetic risk factor for late-onset Alzheimer disease. Previous studies suggest that reduction of apoE levels through genetic manipulation can reduce Aβ pathology. However, it is not clear how reduction of apoE levels after birth would affect amyloid deposition. We utilize an antisense oligonucleotide (ASO) to reduce apoE expression in the brains of APP/PS1-21 mice homozygous for the APOE-ε4 or APOE-ε3 allele. ASO treatment starting after birth led to a significant decrease in Aβ pathology when assessed at 4 months...
December 6, 2017: Neuron
https://www.readbyqxmd.com/read/29204218/interpreting-the-mechanism-of-apoe-p-leu167del-mutation-in-the-incidence-of-familial-hypercholesterolemia-an-in-silico-approach
#11
REVIEW
Omran Mohammed Rashidi, Fatima Amanullah H Nazar, Mohamed Nabil Alama, Zuhier Ahmed Awan
Background: Apolipoprotein E (APOE) gene is a ligand protein in humans which mediates the metabolism of cholesterol by binding to the low-density lipoprotein receptor (LDLR). P.Leu167del mutation in APOE gene was recently connected with Familial Hypercholesterolemia, a condition associated with premature cardiovascular disease. The consequences of this mutation on the protein structure and its receptor binding capacity remain largely unknown. Objective: The current study aims to further decipher the underlying mechanism of this mutation using advanced software-based algorithms...
2017: Open Cardiovascular Medicine Journal
https://www.readbyqxmd.com/read/29203198/phylogeny-and-expression-patterns-of-two-apolipoprotein-e-genes-in-the-flatfish-senegalese-sole
#12
Javier Roman-Padilla, Ana Rodríguez-Rúa, Carlos Carballo, Manuel Manchado, Ismael Hachero-Cruzado
The apolipoprotein E (ApoE) is a key component of several lipoproteins involved in lipid homeostasis. In this study, two cDNA sequences encoding ApoE (referred to as apoEa and apoEb) were characterized in the flatfish Solea senegalensis. The predicted peptides contained conserved structural blocks related with their capacity for lipid binding and lipoprotein receptor interaction. At genomic level, both genes contained five exons and four introns and they were organized into two tandem arrays with apoA-IV gene copies...
December 1, 2017: Gene
https://www.readbyqxmd.com/read/29202360/enhanced-capillary-electrophoretic-screening-of-alzheimer-based-on-direct-apolipoprotein-e-genotyping-and-one-step-multiplex-pcr
#13
Nain Woo, Su-Kang Kim, Yucheng Sun, Seong Ho Kang
Human apolipoprotein E (ApoE) is associated with high cholesterol levels, coronary artery disease, and especially Alzheimer's disease. In this study, we developed an ApoE genotyping and one-step multiplex polymerase chain reaction (PCR) based-capillary electrophoresis (CE) method for the enhanced diagnosis of Alzheimer's. The primer mixture of ApoE genes enabled the performance of direct one-step multiplex PCR from whole blood without DNA purification. The combination of direct ApoE genotyping and one-step multiplex PCR minimized the risk of DNA loss or contamination due to the process of DNA purification...
November 27, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/29191818/sterol-27-hydroxylase-gene-dosage-and-the-anti-atherosclerotic-effect-of-rifampicin-in-mice
#14
Line Zurkinden, Dmitri Sviridov, Bruno Vogt, Geneviève Escher
Sterol 27-hydroxylase (CYP27A1) catalyzes the hydroxylation of cholesterol to 27-hydroxycholesterol (27-OHC) and regulates cholesterol homeostasis. In Cyp27a1/Apolipoprotein E (ApoE) double knockout (KO) mice fed with western diet (WD), the atherosclerotic phenotype found in ApoE KO mice was reversed. As protective mechanism, up-regulation of Cyp3a11 and Cyp7a1 was proposed. Cyp27a1 heterozygote/ ApoE KO (het) mice, with reduced Cyp27a1expression and normal levels of Cyp7a1 and Cyp3a11 , developed more severe lesions than ApoE KO mice...
November 30, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/29183403/linkage-whole-genome-sequence-and-biological-data-implicate-variants-in-rab10-in-alzheimer-s-disease-resilience
#15
Perry G Ridge, Celeste M Karch, Simon Hsu, Ivan Arano, Craig C Teerlink, Mark T W Ebbert, Josue D Gonzalez Murcia, James M Farnham, Anna R Damato, Mariet Allen, Xue Wang, Oscar Harari, Victoria M Fernandez, Rita Guerreiro, Jose Bras, John Hardy, Ronald Munger, Maria Norton, Celeste Sassi, Andrew Singleton, Steven G Younkin, Dennis W Dickson, Todd E Golde, Nathan D Price, Nilüfer Ertekin-Taner, Carlos Cruchaga, Alison M Goate, Christopher Corcoran, JoAnn Tschanz, Lisa A Cannon-Albright, John S K Kauwe
BACKGROUND: While age and the APOE ε4 allele are major risk factors for Alzheimer's disease (AD), a small percentage of individuals with these risk factors exhibit AD resilience by living well beyond 75 years of age without any clinical symptoms of cognitive decline. METHODS: We used over 200 "AD resilient" individuals and an innovative, pedigree-based approach to identify genetic variants that segregate with AD resilience. First, we performed linkage analyses in pedigrees with resilient individuals and a statistical excess of AD deaths...
November 29, 2017: Genome Medicine
https://www.readbyqxmd.com/read/29180857/association-between-apolipoprotein-e-gene-polymorphism-and-mild-cognitive-impairment-a-meta-analysis
#16
Yunxia Jiang, Tao He, Wenshuai Deng, Peng Sun
A number of published case-control studies reported that the apolipoprotein E (ApoE) gene polymorphism was associated with the mild cognitive impairment (MCI). However, previous reports still remain conflicting. To estimate the association between ApoE polymorphism and MCI susceptibility, we searched the electronic databases including PubMed, Wanfang, CNKI (China National Knowledge Infrastructure), VIP, and EMBASE to retrieve all available studies. A total of 18 studies with 2,004 cases and 3,705 controls were included in this meta-analysis...
2017: Clinical Interventions in Aging
https://www.readbyqxmd.com/read/29176964/only-acyl-carrier-protein-1-acpp1-functions-in-pseudomonas-aeruginosa-fatty-acid-synthesis
#17
Jin-Cheng Ma, Yun-Qi Wu, Dan Cao, Wen-Bin Zhang, Hai-Hong Wang
The genome of Pseudomonas aeruginosa contains three open reading frames, PA2966, PA1869, and PA3334, which encode putative acyl carrier proteins, AcpP1, AcpP2, and AcpP3, respectively. In this study, we found that, although these apo-ACPs were successfully phosphopantetheinylated by P. aeruginosa phosphopantetheinyl transferase (PcpS) and all holo-forms of these proteins could be acylated by Vibrio harveyi acyl-ACP synthetase (AasS), only AcpP1 could be used as a substrate for the synthesis of fatty acids, catalyzed by P...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29173597/congenital-heart-disease-and-neurodevelopment-clinical-manifestations-genetics-mechanisms-and-implications
#18
REVIEW
Sarah N Nattel, Laura Adrianzen, Erica C Kessler, Gregor Andelfinger, Mathieu Dehaes, Gabriel Côté-Corriveau, M Pilar Trelles
Children with congenital heart disease (CHD) are at increased risk of neurodevelopmental disorders (NDDs) and psychiatric conditions. These include cognitive, adaptive, motor, speech, behavioural, and executive functioning deficits, as well as autism spectrum disorder and psychiatric conditions. Structural and functional neuroimaging have demonstrated brain abnormalities in young children with CHD before undergoing surgical repair, likely as a result of an in utero developmental insult. Surgical factors do not seem to play a significant role in neurodevelopmental outcomes...
December 2017: Canadian Journal of Cardiology
https://www.readbyqxmd.com/read/29172227/apolipoprotein-e-gene-polymorphism-trauma-burden-and-posttraumatic-stress-symptoms-in-u-s-military-veterans-results-from-the-national-health-and-resilience-in-veterans-study
#19
Natalie P Mota, Shizhong Han, Ilan Harpaz-Rotem, Paul Maruff, John H Krystal, Steven M Southwick, Joel Gelernter, Robert H Pietrzak
BACKGROUND: Previous research examining the association between apolipoprotein E (APOE) gene polymorphism and risk for posttraumatic stress disorder (PTSD) has been inconsistent due to the use of small and select samples. This study examined the relation between APOE genotype and PTSD symptoms in two nationally representative samples of U.S. military veterans. The potential effect of cumulative trauma burden and social support in moderating this association was also evaluated. METHODS: The main sample consisted of 1,386 trauma-exposed European American (EA) veterans (mean age: 62-63 years) who participated in the National Health and Resilience in Veterans Study (NHRVS) in 2011...
November 24, 2017: Depression and Anxiety
https://www.readbyqxmd.com/read/29169989/adamts18-deficiency-leads-to-visceral-adiposity-and-associated-metabolic-syndrome-in-mice
#20
Rui Zhu, Mengting Cheng, Tiantian Lu, Ning Yang, Shuai Ye, Yi-Hsuan Pan, Tao Hong, Suying Dang, Wei Zhang
Visceral adiposity is of greater risk than obesity in subcutaneous adipose tissue for diabetes and cardiovascular disease. Its pathogenesis remains unclear, but it is associated with extracellular matrix (ECM) remodeling. A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTSs) are a family of secreted Zn-dependent metalloproteinases that play crucial roles in development and various diseases owing to their ECM remodeling activity. ADAMTS18 is an "orphan ADAMTS" whose function and substrate remain unclear...
November 20, 2017: American Journal of Pathology
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