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APOE Gene

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https://www.readbyqxmd.com/read/28930654/a-tale-of-two-genes-microglial-apoe-and-trem2
#1
Anna A Pimenova, Edoardo Marcora, Alison M Goate
Microglial cell function is implicated in the etiology of Alzheimer's disease by human genetics. In this issue of Immunity, Krasemann et al. (2017) describe a gene expression signature associated with an APOE- and TREM2-dependent response of microglia to brain tissue damage that accumulates in aging and disease, defining an axis that might be amenable to therapeutic targeting.
September 19, 2017: Immunity
https://www.readbyqxmd.com/read/28930153/selective-hdl-raising-human-apo-a-i-gene-therapy-counteracts-cardiac-hypertrophy-reduces-myocardial-fibrosis-and-improves-cardiac-function-in-mice-with-chronic-pressure-overload
#2
Ruhul Amin, Ilayaraja Muthuramu, Joseph Pierre Aboumsallem, Mudit Mishra, Frank Jacobs, Bart De Geest
Epidemiological studies support an independent inverse association between high-density lipoprotein (HDL) cholesterol levels and heart failure incidence. The effect of selective HDL-raising adeno-associated viral serotype 8-human apolipoprotein (apo) A-I (AAV8-A-I) gene transfer on cardiac remodeling induced by transverse aortic constriction (TAC) was evaluated in C57BL/6 low-density lipoprotein receptor-deficient mice. Septal wall thickness and cardiomyocyte cross-sectional area were reduced by 16.5% (p < 0...
September 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28928671/aerobic-exercise-training-selectively-changes-oxysterol-levels-and-metabolism-reducing-cholesterol-accumulation-in-the-aorta-of-dyslipidemic-mice
#3
Guilherme Silva Ferreira, Paula R Pinto, Rodrigo T Iborra, Vanessa Del Bianco, Monique Fátima Mello Santana, Edna Regina Nakandakare, Valéria S Nunes, Carlos E Negrão, Sergio Catanozi, Marisa Passarelli
Background: Oxysterols are bioactive lipids that control cellular cholesterol synthesis, uptake, and exportation besides mediating inflammation and cytotoxicity that modulate the development of atherosclerosis. Aerobic exercise training (AET) prevents and regresses atherosclerosis by the improvement of lipid metabolism, reverse cholesterol transport (RCT) and antioxidant defenses in the arterial wall. We investigated in dyslipidemic mice the role of a 6-week AET program in the content of plasma and aortic arch cholesterol and oxysterols, the expression of genes related to cholesterol flux and the effect of the exercise-mimetic AICAR, an AMPK activator, in macrophage oxysterols concentration...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28924247/low-level-activity-thresholds-for-changes-in-nmr-biomarkers-and-genes-in-high-risk-subjects-for-type-2-diabetes
#4
Karl-Heinz Herzig, Juhani Leppäluoto, Jari Jokelainen, Emmanuelle Meugnier, Sandra Pesenti, Harri Selänne, Kari A Mäkelä, Riikka Ahola, Timo Jämsä, Hubert Vidal, Sirkka Keinänen-Kiukaanniemi
Our objectives were to determine if there are quantitative associations between amounts and intensities of physical activities (PA) on NMR biomarkers and changes in skeletal muscle gene expressions in subjects with high risk for type 2 diabetes (T2D) performing a 3-month PA intervention. We found that PA was associated with beneficial biomarker changes in a factor containing several VLDL and HDL subclasses and lipids in principal component analysis (P = <0.01). Division of PA into quartiles demonstrated significant changes in NMR biomarkers in the 2nd - 4th quartiles compared to the 1st quartile representing PA of less than 2850 daily steps (P = 0...
September 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28919360/the-roles-of-antimicrobial-peptide-rip-thanatin-in-the-midgut-of-riptortus-pedestris
#5
Kyoung-Eun Park, Seong Han Jang, Junbeom Lee, Seung Ah Lee, Yoshitomo Kikuchi, Young-Su Seo, Bok Luel Lee
Recently, we have reported the structural determination of antimicrobial peptides (AMPs), such as riptocin, rip-defensin, and rip-thanatin, from Riptortus pedestris. However, the biological roles of AMPs in the host midgut remain elusive. Here, we compared the expression levels of AMP genes in apo-symbiotic insects with those of symbiotic insects. Interestingly, the expression level of rip-thanatin was only significantly increased in the posterior midgut region of symbiotic insects. To further determine the role of rip-thanatin, we checked antimicrobial activity in vitro...
September 14, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28919240/single-nucleotide-variants-associated-with-polygenic-hypercholesterolemia-in-families-diagnosed-clinically-with-familial-hypercholesterolemia
#6
Itziar Lamiquiz-Moneo, María Rosario Pérez-Ruiz, Estíbaliz Jarauta, María Teresa Tejedor, Ana M Bea, Rocío Mateo-Gallego, Sofía Pérez-Calahorra, Lucía Baila-Rueda, Victoria Marco-Benedí, Isabel de Castro-Orós, Ana Cenarro, Fernando Civeira
INTRODUCTION AND OBJECTIVES: Approximately 20% to 40% of clinically defined familial hypercholesterolemia cases do not show a causative mutation in candidate genes, and some of them may have a polygenic origin. A cholesterol gene risk score for the diagnosis of polygenic hypercholesterolemia has been demonstrated to be valuable to differentiate polygenic and monogenic hypercholesterolemia. The aim of this study was to determine the contribution to low-density lipoprotein cholesterol (LDL-C) of the single nucleotide variants associated with polygenic hypercholesterolemia in probands with genetic hypercholesterolemia without mutations in candidate genes (nonfamilial hypercholesterolemia genetic hypercholesterolemia) and the genetic score in cascade screening in their family members...
September 14, 2017: Revista Española de Cardiología
https://www.readbyqxmd.com/read/28915562/detecting-the-genetic-link-between-alzheimer-s-disease-and-obesity-using-bioinformatics-analysis-of-gwas-data
#7
Qi-Shuai Zhuang, Hao Zheng, Xiao-Dan Gu, Liang Shen, Hong-Fang Ji
Alzheimer's disease (AD) represents the major form of dementia in the elderly. In recent years, accumulating evidence indicate that obesity may act as a risk factor for AD, while the genetic link between the two conditions remains unclear. This bioinformatics analysis aimed to detect the genetic link between AD and obesity on single nucleotide polymorphisms (SNPs), gene, and pathway levels based on genome-wide association studies data. A total of 31 SNPs were found to be shared by AD and obesity, which were linked to 7 genes...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28912560/the-srgap2-snps-their-haplotypes-and-g%C3%A2-%C3%A3-%C3%A2-e-interactions-on-serum-lipid-traits
#8
Liu Miao, Rui-Xing Yin, Jin-Zhen Wu, Shuo Yang, Wei-Xiong Lin, Shang-Ling Pan
Maonan nationality is a relatively conservative and isolated minority in China. Little is known about the association of the Slit-Robo Rho GTPase activating protein 2 gene (SRGAP2) single nucleotide polymorphisms (SNPs) and serum lipid levels in the Chinese populations. This study was performed to clarify the association of the SRGAP2 rs2483058 and rs2580520 SNPs and their haplotypes with serum lipid traits in the Maonan and Han populations. Genotyping of the 2 SNPs was performed in 2444 unrelated subjects (Han, 1210 and Maonan, 1234) by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28902624/rna-seq-mouse-brain-regions-expression-data-analysis-focus-on-apoe-functional-network
#9
Vladimir N Babenko, Dmitry A Smagin, Natalia N Kudryavtseva
ApoE expression status was proved to be a highly specific marker of energy metabolism rate in the brain. Along with its neighbor, Translocase of Outer Mitochondrial Membrane 40 kDa (TOMM40) which is involved in mitochondrial metabolism, the corresponding genomic region constitutes the neuroenergetic hotspot. Using RNA-Seq data from a murine model of chronic stress a significant positive expression coordination of seven neighboring genes in ApoE locus in five brain regions was observed. ApoE maintains one of the highest absolute expression values genome-wide, implying that ApoE can be the driver of the neighboring gene expression alteration observed under stressful loads...
September 13, 2017: Journal of Integrative Bioinformatics
https://www.readbyqxmd.com/read/28900374/association-between-polymorphisms-in-the-promoter-region-of-the-apolipoprotein-e-apoe-gene-and-alzheimer-s-disease-a-meta-analysis
#10
Hanyan Xiao, Yifeng Gao, Lei Liu, Yan Li
Several studies have evaluated the role of polymorphisms in the promoter region of APOE gene that encodes apolipoprotein E (APOE) and the susceptibility to Alzheimer's disease (AD). The aim of this literature review and meta-analysis was to investigate the relationship between the APOE promoter region single nucleotide polymorphisms (SNPs) (rs449647, -491A/T; rs769446, -427T/C and rs405509 -219T/G) and the risk of developing AD. Eligible controlled studies published up to November 2016 were retrieved from main online scientific and medical databases...
2017: EXCLI journal
https://www.readbyqxmd.com/read/28900020/petrobactin-is-exported-from-bacillus-anthracis-by-the-rnd-type-exporter-apex
#11
A K Hagan, A Tripathi, D Berger, D H Sherman, P C Hanna
Bacillus anthracis-a Gram-positive, spore-forming bacterium-causes anthrax, a highly lethal disease with high bacteremia titers. Such rapid growth requires ample access to nutrients, including iron. However, access to this critical metal is heavily restricted in mammals, which requires B. anthracis to employ petrobactin, an iron-scavenging small molecule known as a siderophore. Petrobactin biosynthesis is mediated by asb gene products, and import of the iron-bound (holo)-siderophore into the bacterium has been well studied...
September 12, 2017: MBio
https://www.readbyqxmd.com/read/28899419/increased-plasma-lipid-levels-exacerbate-muscle-pathology-in-the-mdx-mouse-model-of-duchenne-muscular-dystrophy
#12
Nadia Milad, Zoe White, Arash Y Tehrani, Stephanie Sellers, Fabio M V Rossi, Pascal Bernatchez
BACKGROUND: Duchenne muscular dystrophy (DMD) is caused by loss of dystrophin expression and leads to severe ambulatory and cardiac function decline. However, the dystrophin-deficient mdx murine model of DMD only develops a very mild form of the disease. Our group and others have shown vascular abnormalities in animal models of MD, a likely consequence of the fact that blood vessels express the same dystrophin-associated glycoprotein complex (DGC) proteins as skeletal muscles. METHODS: To test the blood vessel contribution to muscle damage in DMD, mdx (4cv) mice were given elevated lipid levels via apolipoprotein E (ApoE) gene knockout combined with normal chow or lipid-rich Western diets...
September 12, 2017: Skeletal Muscle
https://www.readbyqxmd.com/read/28899010/modelling-apoe-%C3%A9-3-4-allele-associated-sporadic-alzheimer-s-disease-in-an-induced-neuron
#13
Hongwon Kim, Junsang Yoo, Jaein Shin, Yujung Chang, Junghyun Jung, Dong-Gyu Jo, Janghwan Kim, Wonhee Jang, Christopher J Lengner, Byung-Soo Kim, Jongpil Kim
The recent generation of induced neurons by direct lineage conversion holds promise for in vitro modelling of sporadic Alzheimer's disease. Here, we report the generation of induced neuron-based model of sporadic Alzheimer's disease in mice and humans, and used this system to explore the pathogenic mechanisms resulting from the sporadic Alzheimer's disease risk factor apolipoprotein E (APOE) ɛ3/4 allele. We show that mouse and human induced neurons overexpressing mutant amyloid precursor protein in the background of APOE ɛ3/4 allele exhibit altered amyloid precursor protein (APP) processing, abnormally increased production of amyloid-β42 and hyperphosphorylation of tau...
August 1, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28889112/interplay-between-cigarette-smoking-and%C3%A2-pulmonary-reverse-lipid-transport
#14
Éric Jubinville, Maude Talbot, Jean-Christophe Bérubé, Mélanie Hamel-Auger, Michaël Maranda-Robitaille, Marie-Josée Beaulieu, Sophie Aubin, Marie-Ève Paré, David G Kallend, Benoit Arsenault, Yohan Bossé, Mathieu C Morissette
Reverse lipid transport is critical to maintain homeostasis. Smoking causes lipid accumulation in macrophages, therefore suggesting suboptimal reverse lipid transport mechanisms. In this study, we investigated the interplay between smoking and reverse lipid transport and the consequences on smoking-induced lung and peripheral alterations.To investigate the relationship between smoking and reverse lipid transport, we used a clinical lung gene expression dataset and a mouse model of cigarette smoke exposure. We also used ApoA-1(-/-) mice, with reduced reverse lipid transport capacity, and a recombinant ApoA-1 Milano/phospholipid complex (MDCO-216) to boost reverse lipid transport...
September 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28888922/microrna-20a-participates-in-the-aerobic-exercise-based-prevention-of-coronary-artery-disease-by-targeting-pten
#15
Dongwei Wang, Yi Wang, Juan Ma, Wenping Wang, Bingbing Sun, Tengfei Zheng, Ming Wei, Yangli Sun
BACKGROUND: Exercise can reduce the coronary artery disease (CAD) incidence. MiRNA-20a has been reported to distinctly expressed after sustain physical activity. However, its expression and regulation pattern in CAD model with or without exercise has not been reported. OBJECTIVE: In present study, we aim to investigate regulatory mechanism of miR-20a in exercise-associated reduced-CAD incidence and miR-20a-dependent signaling pathways. METHODS: Eight weeks old male ApoE/LDLR double knock out mice were recruited for this study...
September 7, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28888721/tmem106b-and-apoe-polymorphisms-in-chmp2b-mediated-frontotemporal-dementia-ftd-3
#16
Nina Rostgaard, Peter Roos, Esben Budtz-Jørgensen, Peter Johannsen, Gunhild Waldemar, Anne Nørremølle, Suzanne G Lindquist, Susanne Gydesen, Jeremy M Brown, John Collinge, Adrian M Isaacs, Troels T Nielsen, Jørgen E Nielsen
Single-nucleotide polymorphisms in the TMEM106B gene have been identified as a risk factor in frontotemporal dementia (FTD). The major allele of SNP rs3173615 is a risk factor in sporadic FTD, whereas the minor allele seems protective in GRN- and C9orf72-mediated FTD. The role of apolipoprotein E (ApoE) in FTD is uncertain, though an established risk factor in Alzheimer's disease. In a unique Danish family, inherited FTD is caused by a mutation in the CHMP2B gene located on chromosome 3 (FTD-3). In this family, both risk factors TMEM106B and ApoE were analyzed and correlated to age at onset (AAO) and progression in terms of age at institutionalization (AAI) and age at death (AAD)...
July 11, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28887372/the-apolipoprotein-c-iii-gln38lys-variant-associated-with-human-hypertriglyceridemia-is-a-gain-of-function-mutation
#17
Meenakshi Sundaram, Kaitlin R Curtis, Mohsen Amir Alipour, Nicholas D LeBlond, Kaitlyn D Margison, Rebecca A Yaworski, Robin J Parks, Adam D McIntyre, Robert A Hegele, Morgan D Fullerton, Zemin Yao
Recent cell culture and animal studies have suggested expression of human apolipoprotein (apo) C-III in the liver has a profound impact on the triacylglycerol (TAG)-rich VLDL1 production under lipid-rich conditions. The apoC-III Gln38Lys variant was identified in subjects of Mexican origin with moderate hypertriglyceridemia. We postulated that Gln38Lys (C3QK), being a gain-of-function mutation, promotes hepatic VLDL1 assembly/secretion. To test this hypothesis, we expressed C3QK in McA-RH7777 cells and apoc3-null mice to contrast its effect with wildtype apoC-III (C3WT)...
September 8, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28883857/postmenopausal-cognitive-changes-and-androgen-levels-in-the-context-of-apolipoprotein-e-polymorphism
#18
Iwona Bojar, Jarosław Pinkas, Mariusz Gujski, Alfred Owoc, Dorota Raczkiewicz, Kasia Gustaw-Rothenberg
INTRODUCTION: The focus of this study was to assess cognitive functions in relation to androgens and specifically testosterone and dehydroepiandrosterone in postmenopausal women as well as the correlation between cognitive functions and these two androgens according to polymorphism of the apolipoprotein E gene (APOE). MATERIAL AND METHODS: A group of 402 women was recruited to the study (minimum 2 years after the last menstruation, follicle-stimulating hormone (FSH) more than 30 U/ml and no dementia signs on Montreal Cognitive Assessment)...
August 2017: Archives of Medical Science: AMS
https://www.readbyqxmd.com/read/28864445/dissection-of-the-molecular-circuitry-controlling-virulence-in-francisella-tularensis
#19
Bonnie J Cuthbert, Wilma Ross, Amy E Rohlfing, Simon L Dove, Richard L Gourse, Richard G Brennan, Maria A Schumacher
Francisella tularensis, the etiological agent of tularemia, is one of the most infectious bacteria known. Because of its extreme pathogenicity, F. tularensis is classified as a category A bioweapon by the US government. F. tularensis virulence stems from genes encoded on the Francisella pathogenicity island (FPI). An unusual set of Francisella regulators-the heteromeric macrophage growth locus protein A (MglA)-stringent starvation protein A (SspA) complex and the DNA-binding protein pathogenicity island gene regulator (PigR)-activates FPI transcription and thus is essential for virulence...
September 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/28861889/red-yeast-rice-prevents-atherosclerosis-through-regulating-inflammatory-signaling-pathways
#20
Min Wu, Wen-Gao Zhang, Long-Tao Liu
OBJECTIVE: To observe the effects of red yeast rice (RYR) on blood lipid levels, aortic atherosclerosis (AS), and plaque stability in apolipoprotein E gene knockout (ApoE-/-) mice. METHODS: Twenty-four ApoE-/- mice were fed with a high-fat diet starting from 6 weeks of age. Mice were randomized into three groups (n = 8 in each group): model group (ApoE-/- group), RYR group (ApoE-/- + RYR group), and simvastatin group (ApoE-/- + simvastatin group). Eight 6-week-old C57BL/6 mice were assigned as the control group and fed with a basic diet...
September 2017: Chinese Journal of Integrative Medicine
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