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APOE Gene

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https://www.readbyqxmd.com/read/29143599/epistasis-physical-capacity-related-genes-and-exceptional-longevity-fndc5-gene-interactions-with-candidate-genes-foxoa3-and-apoe
#1
Noriyuki Fuku, Roberto Díaz-Peña, Yasumichi Arai, Yukiko Abe, Hirofumi Zempo, Hisashi Naito, Haruka Murakami, Motohiko Miyachi, Carlos Spuch, José A Serra-Rexach, Enzo Emanuele, Nobuyoshi Hirose, Alejandro Lucia
BACKGROUND: Forkhead box O3A (FOXOA3) and apolipoprotein E (APOE) are arguably the strongest gene candidates to influence human exceptional longevity (EL, i.e., being a centenarian), but inconsistency exists among cohorts. Epistasis, defined as the effect of one locus being dependent on the presence of 'modifier genes', may contribute to explain the missing heritability of complex phenotypes such as EL. We assessed the potential association of epistasis among candidate polymorphisms related to physical capacity, as well as antioxidant defense and cardiometabolic traits, and EL in the Japanese population...
November 14, 2017: BMC Genomics
https://www.readbyqxmd.com/read/29132311/weighted-gene-co-expression-network-analysis-of-expression-data-of-monozygotic-twins-identifies-specific-modules-and-hub-genes-related-to-bmi
#2
Weijing Wang, Wenjie Jiang, Lin Hou, Haiping Duan, Yili Wu, Chunsheng Xu, Qihua Tan, Shuxia Li, Dongfeng Zhang
BACKGROUND: The therapeutic management of obesity is challenging, hence further elucidating the underlying mechanisms of obesity development and identifying new diagnostic biomarkers and therapeutic targets are urgent and necessary. Here, we performed differential gene expression analysis and weighted gene co-expression network analysis (WGCNA) to identify significant genes and specific modules related to BMI based on gene expression profile data of 7 discordant monozygotic twins. RESULTS: In the differential gene expression analysis, it appeared that 32 differentially expressed genes (DEGs) were with a trend of up-regulation in twins with higher BMI when compared to their siblings...
November 13, 2017: BMC Genomics
https://www.readbyqxmd.com/read/29129602/standardized-fraction-of-xylocarpus-moluccensis-fruits-improve-vascular-relaxation-and-plaque-stability-in-dyslipidemic-models-of-atherosclerosis
#3
Jitendra S Kanshana, Sanjay C Rebello, Priya Pathak, Babu Nageswararao Kanuri, Hobby Aggarwal, Vasundhara Srivastava, Vivek Khanna, Vishal Singh, Kumaravelu Jagavelu, Manoj K Barthwal, Madhu Dikshit
ETHNOPHARMACOLOGICAL RELEVANCE: Xylocarpus moluccensis (Lamk.) M. Roem of family Meliaceae has triterpenoids rich fruits. Triterpenoids have been known to possess cardioprotection and anti-atherosclerotic activities (Han and Bakovic, 2015; Wu et al., 2009). Standardised fraction of these fruits exhibited anti-dyslipidemic (Srivastava et al., 2015), anti-inflammatory (Ravangpai et al., 2011) and CNS depressant activity (Sarker et al., 2007). However, there is no report in the literature on its cardiovascular effects...
November 9, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29128090/crocus-sativus-l-aqueous-extract-reduces-atherogenesis-increases-atherosclerotic-plaque-stability-and-improves-glucose-control-in-diabetic-atherosclerotic-animals
#4
Ei Christodoulou, N P E Kadoglou, M Stasinopoulou, O A Konstandi, C Kenoutis, Z I Kakazanis, A Rizakou, N Kostomitsopoulos, G Valsami
BACKGROUND AND AIMS: We aimed to evaluate a possible atheroprotective effect of saffron aqueous extract (SFE), and its potential anti-inflammatory mechanisms, in apoE knockout (ApoE(-/-)) mice. METHODS: Fifty male, ApoE(-/-) mice, fed a high-fat diet (HFD) for 12 weeks, were randomized into 5 groups: (1) baseline group, euthanatized, without intervention, (2) three saffron groups, receiving HFD and 30,60,90 mg/kg/day of SFE, respectively, for four weeks, per os through gavage, after reconstitution in water for injection (WFI), (3) control group (COG), receiving daily HFD and the same volume of WFI (four weeks)...
November 1, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/29125573/tailoring-nutritional-advice-for-mexicans-based-on-prevalence-profiles-of-diet-related-adaptive-gene-polymorphisms
#5
Claudia Ojeda-Granados, Arturo Panduro, Karina Gonzalez-Aldaco, Maricruz Sepulveda-Villegas, Ingrid Rivera-Iñiguez, Sonia Roman
Diet-related adaptive gene (DRAG) polymorphisms identified in specific populations are associated with chronic disorders in carriers of the adaptive alleles due to changes in dietary and lifestyle patterns in recent times. Mexico's population is comprised of Amerindians (AM) and Mestizos who have variable AM, European (EUR) and African genetic ancestry and an increased risk of nutrition-related chronic diseases. Nutritional advice based on the Mexican genome and the traditional food culture is needed to develop preventive and therapeutic strategies...
November 10, 2017: Journal of Personalized Medicine
https://www.readbyqxmd.com/read/29124426/molecular-chaperones-involved-in-mitochondrial-iron-sulfur-protein-biogenesis
#6
REVIEW
Rafal Dutkiewicz, Malgorzata Nowak
Iron-sulfur (FeS) clusters are prosthetic groups critical for the function of many proteins in all domains of life. FeS proteins function in processes ranging from oxidative phosphorylation and cofactor biosyntheses to DNA/RNA metabolism and regulation of gene expression. In eukaryotic cells, mitochondria play a central role in the process of FeS biogenesis and support maturation of FeS proteins localized within mitochondria and in other cellular compartments. In humans, defects in mitochondrial FeS cluster biogenesis lead to numerous pathologies, which are often fatal...
November 9, 2017: Journal of Biological Inorganic Chemistry: JBIC
https://www.readbyqxmd.com/read/29124110/characterization-of-apoe-and-tomm40-allele-frequencies-in-the-japanese-population
#7
Akira Nishimura, Hidenori Nonomura, Shingo Tanaka, Michihiro Yoshida, Yuka Maruyama, Yutaka Aritomi, Ann M Saunders, Daniel K Burns, Michael W Lutz, Grant Runyan, Eric Lai, Kumar Budur, Allen D Roses
Introduction: Dementia is one of the major health threats to our aging society, and Alzheimer's disease (AD) is the leading cause. In Japan, ∼15% of the elderly population has dementia. The apolipoprotein E (APOE) genotype and a polymorphism (rs10524523) in the translocase of outer mitochondrial membrane 40 (TOMM40) gene have been associated with the age of onset of AD. However, differences in allele frequencies of these markers in different ethnic populations are not well known. Methods: Whole blood samples were collected from 300 Japanese subjects, and genomic DNA was extracted to determine APOE alleles and TOMM40 rs10524523 genotypes...
November 2017: Alzheimer's & Dementia: Translational Research & Clinical Interventions
https://www.readbyqxmd.com/read/29122817/apo-a-i-apolipoprotein-a-i-vascular-gene-therapy-provides-durable-protection-against-atherosclerosis-in-hyperlipidemic-rabbits
#8
Bradley K Wacker, Nagadhara Dronadula, Lianxiang Bi, Alexis Stamatikos, David A Dichek
OBJECTIVE: Gene therapy that expresses apo A-I (apolipoprotein A-I) from vascular wall cells has promise for preventing and reversing atherosclerosis. Previously, we reported that transduction of carotid artery endothelial cells with a helper-dependent adenoviral (HDAd) vector expressing apo A-I reduced early (4 weeks) fatty streak development in fat-fed rabbits. Here, we tested whether the same HDAd could provide long-term protection against development of more complex lesions. APPROACH AND RESULTS: Fat-fed rabbits (n=25) underwent bilateral carotid artery gene transfer, with their left and right common carotids randomized to receive either a control vector (HDAdNull) or an apo A-I-expressing vector (HDAdApoAI)...
November 9, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29117956/snps-in-a%C3%AE-clearance-proteins-lower-csf-a%C3%AE-1-42-levels-and-earlier-onset-of-dementia-in-pd
#9
Kathrin Brockmann, Stefanie Lerche, Sarah Selina Dilger, Johannes Georg Stirnkorb, Anja Apel, Ann-Kathrin Hauser, Inga Liepelt-Scarfone, Daniela Berg, Thomas Gasser, Claudia Schulte, Walter Maetzler
OBJECTIVE: To evaluate whether genetic variants in β-amyloid (Aβ) clearance proteins are associated with CSF levels of Aβ1-42 on a biological level and the onset of dementia on a clinical level in Parkinson disease (PD). METHODS: We analyzed genetic variants known to be involved in Aβ clearance in a PD group comprising 456 patients, 103 of them with dementia. Single nucleotide polymorphisms in the genes APOE, cystatin C (CST), and membrane metalloendopeptidase (MME) were evaluated in relation to demographic variables, clinical phenotypes, and CSF Aβ1-42 levels using a cross-sectional approach...
November 8, 2017: Neurology
https://www.readbyqxmd.com/read/29114222/ginsenoside-rb1-enhances-atherosclerotic-plaque-stability-by-improving-autophagy-and-lipid-metabolism-in-macrophage-foam-cells
#10
Lei Qiao, Xue Zhang, Minghao Liu, Xiaoling Liu, Mei Dong, Jing Cheng, Xinyu Zhang, Chungang Zhai, Yu Song, Huixia Lu, Wenqiang Chen
Atherosclerosis (AS) is a lipid-driven disease in which macrophage foam cells play a critical role by increasing vascular lipid accumulation and contributing to plaque instability. Ginsenoside Rb1 (Rb1), the most abundant active component of ginseng, has been found potently to promote lipid metabolism and attenuate lipid accumulation. However, the underlying mechanisms remain unclear. In this study, the effects of Rb1 on lipid accumulation and plaque stability were investigated both in vitro and in vivo by using primary peritoneal macrophages isolated from C57BL/6 mice and an AS model in ApoE(-/-) mice...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29107063/hidden-heterogeneity-in-alzheimer-s-disease-insights-from-genetic-association-studies-and-other-analyses
#11
Anatoliy I Yashin, Fang Fang, Mikhail Kovtun, Deqing Wu, Matt Duan, Konstantin Arbeev, Igor Akushevich, Alexander Kulminski, Irina Culminskaya, Ilya Zhbannikov, Arseniy Yashkin, Eric Stallard, Svetlana Ukraintseva
Despite evident success in clarifying many important features of Alzheimer's disease (AD) the efficient methods of its prevention and treatment are not yet available. The reasons are likely to be the fact that AD is a multifactorial and heterogeneous health disorder with multiple alternative pathways of disease development and progression. The availability of genetic data on individuals participated in longitudinal studies of aging health and longevity, as well as on participants of cross-sectional case-control studies allow for investigating genetic and non-genetic connections with AD and to link the results of these analyses with research findings obtained in clinical, experimental, and molecular biological studies of this health disorder...
October 26, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/29103864/apolipoprotein-e-gene-polymorphism-and-subclinical-carotid-atherosclerosis-the-northern-manhattan-study
#12
Brett Doliner, Chuanhui Dong, Susan H Blanton, Hannah Gardener, Mitchell S V Elkind, Ralph L Sacco, Ryan T Demmer, Moise Desvarieux, Tatjana Rundek
BACKGROUND: Apolipoprotein E (APOE) polymorphism has previously been associated with carotid intima-media thickness (cIMT) in predominantly Caucasian populations. We sought to test the strength of the relationship between APOE-ε4 carrier status and subclinical atherosclerosis in a tri-ethnic population with a large Hispanic representation. METHODS: We assessed the association between APOE polymorphism and cIMT and plaque burden among 1243 stroke-free individuals (mean age 69 years, 65% Hispanic, 18% black, 17% white) using a sequence of multivariable regression models...
November 2, 2017: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
https://www.readbyqxmd.com/read/29103623/polygenic-risk-score-in-postmortem-diagnosed-sporadic-early-onset-alzheimer-s-disease
#13
Sultan Chaudhury, Tulsi Patel, Imelda S Barber, Tamar Guetta-Baranes, Keeley J Brookes, Sally Chappell, James Turton, Rita Guerreiro, Jose Bras, Dena Hernandez, Andrew Singleton, John Hardy, David Mann, Kevin Morgan
Sporadic early-onset Alzheimer's disease (sEOAD) exhibits the symptoms of late-onset Alzheimer's disease but lacks the familial aspect of the early-onset familial form. The genetics of Alzheimer's disease (AD) identifies APOEε4 to be the greatest risk factor; however, it is a complex disease involving both environmental risk factors and multiple genetic loci. Polygenic risk scores (PRSs) accumulate the total risk of a phenotype in an individual based on variants present in their genome. We determined whether sEOAD cases had a higher PRS compared to controls...
October 10, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29103206/novel-approaches-for-hdl-directed-therapies
#14
REVIEW
Jacques Genest, Hong Y Choi
PURPOSE OF REVIEW: High-density lipoproteins (HDL) are thought to exert a protective role against atherosclerosis. The measurement of the cholesterol mass within HDL (HDL-C) represents a good biomarker of cardiovascular health, but HDL-C appears to be a poor therapeutic target. Here, we discuss new targets for the development of HDL-directed therapies. RECENT FINDINGS: Among cardio-protective functions of HDL particles, the ability of HDL to remove cholesterol from cells involved in the early stages of atherosclerosis is considered one of the most important functions...
November 4, 2017: Current Atherosclerosis Reports
https://www.readbyqxmd.com/read/29098831/-effect-of-dracocephalum-moldavica-total-flavones-on-expression-of-tgf-%C3%AE-1-smad-signaling-pathway-and-matrix-metalloproteinase-of-atherosclerosis-apoe-mice
#15
Yang Liu, Yi-Ning Quan, Xin-Chun Wang, Xin-Hong Guo, Yong Yuan, Wen-Jiang Cao, Jiang Cheng
To investigate the effect and mechanism of Dracocephalum moldovica total flavones (TFDM) on the formation of atherosclerosis ApoE-/- mice induced by high fat diet. A total of 40 SPF 8-week-old male ApoE-/- mice were fed with high fat diet and randomly divided into 5 groups. TFDM high, medium, low-dose group were given 21, 42, 84 mg•kg⁻¹•d⁻¹ by gavage; Simvastatin group was fed with simvastatin 3.5 mg•kg⁻¹•d⁻¹; and model group was given the same dose of normal saline. The other eight male C57BL/6J mice of the same genetic background and age were set up as control group and fed with common diet...
July 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/29098550/enteric-glial-dysfunction-evoked-by-apolipoprotein-e-deficiency-contributes-to-delayed-gastric-emptying
#16
Seiichiro Fukuhara, Tatsuhiro Masaoka, Soraya Nishimura, Masaya Nakamura, Juntaro Matsuzaki, Hitoshi Tsugawa, Sawako Miyoshi, Hideki Mori, Satoshi Kawase, Shinsuke Shibata, Hideyuki Okano, Takanori Kanai, Hidekazu Suzuki
BACKGROUND AND AIM: Diabetes is the main cause of gastroparesis accompanying decreased neuronal nitric oxide synthase (nNOS) in myenteric ganglia of the stomach. Decreased nNOS expression in the stomach also results from defects in apolipoprotein E (ApoE), which is secreted by astrocytes and has neuroprotective effects on the central nervous system. However, the roles of ApoE and enteric glial cells on gastric motility are uncertain. In this study, ApoE and enteric glial cell alterations in gastroparesis were investigated...
November 2, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/29098407/cytoprotective-effects-of-transgenic-neuroglobin-overexpression-in-an-acute-and-chronic-mouse-model-of-ischemic-heart-disease
#17
Evi Luyckx, Bert R Everaert, Bieke Van der Veken, Wendy Van Leuven, Jean-Pierre Timmermans, Christiaan J Vrints, Guido R Y De Meyer, Wim Martinet, Sylvia Dewilde
Neuroglobin (NGB) is an oxygen-binding protein that is mainly expressed in nervous tissues where it is considered to be neuroprotective during ischemic brain injury. Interestingly, transgenic mice overexpressing NGB reveal cytoprotective effects on tissues lacking endogenous NGB, which might indicate a therapeutic role for NGB in a broad range of ischemic conditions. In the present study, we investigated the effect of NGB overexpression on survival as well as on the size and occurrence of myocardial infarctions (MI) in a mouse model of acute MI (AMI) and a model of advanced atherosclerosis (ApoE (-/-) Fbn1 (C1039G+/-) mice), in which coronary plaques and MI develop in mice being fed a Western-type diet...
November 2, 2017: Heart and Vessels
https://www.readbyqxmd.com/read/29096837/the-role-of-antisense-oligonucleotide-therapy-against-apolipoprotein-ciii-in-hypertriglyceridemia
#18
Ioanna Gouni-Berthold
Increased triglyceride levels (higher than ∼1000 mg/dL) are associated with an increased risk for pancreatitis. Apolipoprotein-CIII (apo-CIII) plays a key role in the metabolism of triglycerides and triglyceride-rich lipoproteins. While loss of function mutations in the gene encoding apo-CIII (APOC3) are associated with low triglyceride levels and a decreased risk for cardiovascular disease (CVD), overexpression of APOC3 is associated with hypertriglyceridemia. Although many drugs such as fibrates, statins and omega-3 fatty acids modestly decrease triglyceride levels (and apo-CIII concentrations), there are many patients who still have severe hypertriglyceridemia and are at risk for pancreatitis and potentially CVD...
November 2017: Atherosclerosis. Supplements
https://www.readbyqxmd.com/read/29096742/hmgcr-and-apoe-mutations-may-cause-different-responses-to-lipid-lowering-statin-therapy
#19
D Kirac, E Bayam, M Dagdelen, H Gezmis, S Sarikaya, S Pala, E C Altunok, E Genc
Coronary artery disease (CAD) and its complications are the major causes of death in the world. Although statins have been used to lower lipid levels in CAD patients, this goal can not be attained in 1/3 of the patients. The objective of this study was to investigate whether common variations in HMG-CoA Reductase(HMGCR) and Apolipoprotein E (ApoE) genes involved in lipid and statin metabolism modify the effect of statins on serum lipid and lipoprotein concentrations in CAD patients.A hundred  CAD patients were enrolled into the study...
October 31, 2017: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/29089350/unspliced-xbp1-confers-vsmc-homeostasis-and-prevents-aortic-aneurysm-formation-via-foxo4-interaction
#20
Guizhen Zhao, Yi Fu, Zeyu Cai, Fang Yu, Ze Gong, Rongbo Dai, Yanhua Hu, Lingfang Zeng, Qingbo Xu, Wei Kong
Rationale: Although not fully understood, the phenotypic transition of vascular smooth muscle cells exhibits at the early onset of the pathology of aortic aneurysms. Exploring the key regulators that are responsible for maintaining the contractile phenotype of VSMCs may confer vascular homeostasis and prevent aneurysmal disease. X-box binding protein 1, which exists in a transcriptionally inactive unspliced form (XBP1u) and a spliced active form (XBP1s), is a key component in response to endoplasmic reticular (ER) stress...
October 31, 2017: Circulation Research
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