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APOE Gene

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https://www.readbyqxmd.com/read/28527212/apolipoprotein-e4-gender-body-mass-index-inflammation-insulin-resistance-and-air-pollution-interactions-recipe-for-alzheimer-s-disease-development-in-mexico-city-young-females
#1
Lilian Calderón-Garcidueñas, Suzanne M de la Monte
Given the epidemiological trends of increasing Alzheimer's disease (AD) and growing evidence that exposure and lifestyle factors contribute to AD risk and pathogenesis, attention should be paid to variables such as air pollution, in order to reduce rates of cognitive decline and dementia. Exposure to fine particulate matter (PM2.5) and ozone (O3) above the US EPA standards is associated with AD risk. Mexico City children experienced pre- and postnatal high exposures to PM2.5, O3, combustion-derived iron-rich nanoparticles, metals, polycyclic aromatic hydrocarbons, and endotoxins...
May 17, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28523739/mechanisms-of-peptide-sex-pheromone-regulation-of-conjugation-in-enterococcus-faecalis
#2
Yuqing Chen, Arpan Bandyopadhyay, Briana K Kozlowicz, Heather A H Haemig, Albert Tai, Wei-Shou Hu, Gary M Dunny
In many gram positive bacteria, horizontal transfer and virulence are regulated by peptide-mediated cell-cell signaling. The heptapeptide cCF10 (C) activates conjugative transfer of the Enterococcus faecalis plasmid pCF10, whereas the iCF10 (I) peptide inhibits transfer. Both peptides bind to the same domain of the master transcription regulator PrgX, a repressor of transcription of the prgQ operon encoding conjugation genes. We show that repression of prgQ by PrgX tetramers requires formation of a pCF10 DNA loop where each of two PrgX DNA-binding sites is occupied by a dimer...
May 19, 2017: MicrobiologyOpen
https://www.readbyqxmd.com/read/28517938/glutamate-ligation-in-the-ni-ii-and-co-ii-responsive-escherichia-coli-transcriptional-regulator-rcnr
#3
Carolyn E Carr, Francesco Musiani, Hsin-Ting Huang, Peter T Chivers, Stefano Ciurli, Michael J Maroney
Escherichia coli RcnR (resistance to cobalt and nickel regulator, EcRcnR) is a metal-responsive repressor of the genes encoding the Ni(II) and Co(II) exporter proteins RcnAB by binding to PRcnAB. The DNA binding affinity is weakened when the cognate ions Ni(II) and Co(II) bind to EcRcnR in a six-coordinate site that features a (N/O)5S ligand donor-atom set in distinct sites: while both metal ions are bound by the N terminus, Cys35, and His64, Co(II) is additionally bound by His3. On the other hand, the noncognate Zn(II) and Cu(I) ions feature a lower coordination number, have a solvent-accessible binding site, and coordinate protein ligands that do not include the N-terminal amine...
May 18, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28512139/a-genome-wide-association-meta-analysis-on-lipoprotein-a-concentrations-adjusted-for-apolipoprotein-a-isoforms
#4
Salome Mack, Stefan Coassin, Rico Rueedi, Noha A Yousri, Ilkka Seppälä, Christian Gieger, Sebastian Schönherr, Lukas Forer, Gertraud Erhart, Pedro Marques-Vidal, Janina Ried, Gerard Waeber, Sven Bergmann, Doreen Dähnhardt, Andrea Stöckl, Olli T Raitakari, Mika Kähönen, Annette Peters, Thomas Meitinger, Konstantin Strauch, Ludmilla Kedenko, Bernhard Paulweber, Terho Lehtimäki, Steven C Hunt, Peter Vollenweider, Claudia Lamina, Florian Kronenberg
High lipoprotein(a) [Lp(a)] concentrations are an independent risk factor for cardiovascular outcomes. Concentrations are strongly influenced by apo(a) KIV repeat isoforms. We aimed to identify genetic loci associated with Lp(a) concentrations using data from five genome-wide association studies (n=13,781). We identified 48 independent SNPs in the LPA and 1 SNP in the APOE gene region to be significantly associated with Lp(a) concentrations. We also adjusted for apo(a) isoforms to identify loci affecting Lp(a) levels independently from them, which resulted in 31 SNPs (30 in the LPA, 1 in the APOE gene region)...
May 16, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28508969/five-year-follow-up-of-a-case-of-lipoprotein-glomerulopathy-with-apoe-kyoto-mutation
#5
Ryosuke Usui, Masaki Takahashi, Kosaku Nitta, Minako Koike
We report the case of a 34-year-old Japanese male with lipoprotein glomerulopathy (LPG). Renal biopsy showed LPG, and followed by a genetic analysis revealed a mutation in apolipoprotein E gene (APOE Kyoto; Arg25Cys). We started treatment with probucol, bezafibrate, losartan, and allopurinol. Urinary protein decreased in response to treatment but has remained at about 1.27 ± 0.71 g/gCr, and a repeat biopsy which was performed 1 year after the first biopsy showed no clear evidence of pathological remission and complication of other glomerular disease...
November 2016: CEN Case Reports
https://www.readbyqxmd.com/read/28505974/state-of-play-in-alzheimer-s-disease-genetics
#6
Jin-Bao Zhu, Chen-Chen Tan, Lan Tan, Jin-Tai Yu
Alzheimer's disease (AD), the main form of dementia in the elderly, is the most common progressive neurodegenerative disease characterized by rapidly progressive cognitive dysfunction and behavior impairment. AD exhibits a considerable heritability and great advances have been made in approaches to searching the genetic etiology of AD. In AD genetic studies, methods have developed from classic linkage-based and candidate-gene-based association studies to genome-wide association studies (GWAS) and next generation sequencing...
May 11, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28504688/accelerated-atherosclerosis-development-in-c57bl6-mice-by-overexpressing-aav-mediated-pcsk9-and-partial-carotid-ligation
#7
Sandeep Kumar, Dong-Won Kang, Amir Rezvan, Hanjoong Jo
Studying the role of a particular gene in atherosclerosis typically requires a time-consuming and often difficult process of generating double knockouts or transgenics on ApoE(-/-) or LDL receptor (LDLR)(-/-) background. Recently, it was reported that adeno-associated-virus-8 (AAV8)-mediated overexpression of PCSK9 (AAV8-PCSK9) rapidly induced hyperlipidemia. However, using this method in C57BL6 wild-type (C57) mice, it took ~3 months to develop atherosclerosis. Our partial carotid ligation model is used to rapidly develop atherosclerosis by inducing disturbed flow in the left common carotid artery within 2 weeks in ApoE(-/-) or LDLR(-/-) mice...
May 15, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28502803/gene-co-expression-networks-identify-trem2-and-tyrobp-as-major-hubs-in-human-apoe-expressing-mice-following-traumatic-brain-injury
#8
Emilie L Castranio, Anais Mounier, Cody M Wolfe, Kyong Nyon Nam, Nicholas F Fitz, Florent Letronne, Jonathan Schug, Radosveta Koldamova, Iliya Lefterov
Traumatic brain injury (TBI) is strongly linked to an increased risk of developing dementia, including chronic traumatic encephalopathy and possibly Alzheimer's disease (AD). APOEε4 allele of human Apolipoprotein E (APOE) gene is the major genetic risk factor for late onset AD and has been associated with chronic traumatic encephalopathy and unfavorable outcome following TBI. To determine if there is an APOE isoform-specific response to TBI we performed controlled cortical impact on 3-month-old mice expressing human APOE3 or APOE4 isoforms...
May 11, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28502043/different-hippocampus-functional-connectivity-patterns-in-healthy-young-adults-with-mutations-of-app-presenilin-1-2-and-apoe%C3%AE%C2%B54
#9
Li Juan Zheng, Yun Yan Su, Yun Fei Wang, U Joseph Schoepf, Akos Varga-Szemes, Jonathan Pannell, Xue Liang, Gang Zheng, Guang Ming Lu, Gui Fen Yang, Long Jiang Zhang
This study aims to explore the hippocampus-based functional connectivity patterns in young, healthy APP and/or presenilin-1/2 mutation carriers and APOE ε4 subjects. Seventy-eight healthy young adults (33 male, mean age 24.0 ± 2.2 years; 18 APP and/or presenilin1/2 mutation carriers [APP/presenilin-1/2 group], 30 APOE ε4 subjects [APOE ε4 group], and 30 subjects without the above-mentioned genes [control group]) underwent resting-state functional MR imaging and neuropsychological assessments. Bilateral hippocampus functional connectivity patterns were compared among three groups...
May 13, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28492976/squalene-promotes-cholesterol-homeostasis-in-macrophage-and-hepatocyte-cells-via-activation-of-liver-x-receptor-lxr-%C3%AE-and-%C3%AE
#10
Hoang Thi Minh Hien, Nguyen Cam Ha, Le Thi Thom, Dang Diem Hong
OBJECTIVE: To examine the effect of squalene on liver X receptors (LXRs) that regulate target genes associated with reverse cholesterol transport and thus control whole-body cholesterol homeostasis. RESULTS: To examine the effect of squalene on liver X receptors (LXRs) that regulate target genes associated with reverse cholesterol transport and thus control whole-body cholesterol homeostasis. Squalene significantly stimulated the transactivation of liver X receptor modulator LXRα and LXRβ...
May 10, 2017: Biotechnology Letters
https://www.readbyqxmd.com/read/28492093/higher-prevalence-of-cerebral-white-matter-hyperintensities-in-homozygous-apoe-%C3%A9-4-allele-carriers-aged-45-75-results-from-the-alfa-study
#11
Santiago Rojas, Anna Brugulat-Serrat, Nuria Bargalló, Carolina Minguillón, Alan Tucholka, Carles Falcon, Andreia Carvalho, Sebastian Morán, Manel Esteller, Nina Gramunt, Karine Fauria, Jordi Camí, José L Molinuevo, Juan D Gispert
Cerebral white matter hyperintensities are believed the consequence of small vessel disease and are associated with risk and progression of Alzheimer's disease. The ɛ4 allele of the APOE gene is the major factor accountable for Alzheimer's disease heritability. However, the relationship between white matter hyperintensities and APOE genotype in healthy subjects remains controversial. We investigated the association between APOE-ɛ4 and vascular risk factors with white matter hyperintensities, and explored their interactions, in a cohort of cognitively healthy adults (45-75 years)...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28488677/uninformed-consent-in-nutrigenomic-research
#12
A Cecile Jw Janssens, Eline M Bunnik, Wylie Burke, Maartje Hn Schermer
Genetic testing for personalizing diet and wellness programs is performed without extensive counseling that informs about the potential implications of knowing one's genotype status. Genetic counseling seems redundant for genes that impact the effect of diet on biomarkers such as cholesterol and blood pressure, but the same genes may have pleiotropic effects that cannot be ignored. A well-known example is the APOE gene, which is implicated in cholesterol regulation and is a major risk factor for Alzheimer's disease...
May 10, 2017: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/28487499/updated-meta-analysis-of-the-role-of-apoe-%C3%AE%C2%B52-%C3%AE%C2%B53-%C3%AE%C2%B54-alleles-in-frontotemporal-lobar-degeneration
#13
Wen-Hua Su, Zhi-Hong Shi, Shu-Ling Liu, Xiao-Dan Wang, Shuai Liu, Yong Ji
We performed an updated meta-analysis to assess the role of the ε2/ε3/ε4 alleles of Apolipoprotein E gene (APOE) in frontotemporal lobar degeneration (FTLD). The relevant articles were retrieved from PubMed, CENTRAL, EMBASE and Web of Science databases, and 51 eligible case-control studies with 5123 cases and 20566 controls were selected after screening according to inclusion and exclusion criteria. Our analysis demonstrated that APOE ε4 was associated with increased FTLD risk in all genetic models (ε4 vs...
April 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28487392/epha2-expression-regulates-inflammation-and-fibroproliferative-remodeling-in-atherosclerosis
#14
Alexandra C Finney, Steven D Funk, Jonette Green, Arif Yurdagul, Mohammad A Rana, Rebecca Pistorius, Miriam Henry, Andrew D Yurochko, Christopher B Pattillo, James G Traylor, Jin Chen, Matthew D Woolard, Christopher G Kevil, A Wayne Orr
Background -Atherosclerotic plaque formation results from chronic inflammation and fibroproliferative remodeling in the vascular wall. We previously demonstrated that both human and mouse atherosclerotic plaques show elevated expression of EphA2, a guidance molecule involved in cell-cell interactions and tumorigenesis. Methods -Here, we assessed EphA2's role in atherosclerosis by deleting EphA2 in a mouse model of atherosclerosis (Apoe(-/-)) and by assessing EphA2 function in multiple vascular cell culture models...
May 9, 2017: Circulation
https://www.readbyqxmd.com/read/28483459/animal-models-of-atherosclerosis
#15
Besa Emini Veseli, Paola Perrotta, Gregory R A De Meyer, Lynn Roth, Carole Van der Donckt, Wim Martinet, Guido R Y De Meyer
An ideal animal model of atherosclerosis resembles human anatomy and pathophysiology and has the potential to be used in medical and pharmaceutical research to obtain results that can be extrapolated to human medicine. Moreover, it must be easy to acquire, can be maintained at a reasonable cost, is easy to handle and shares the topography of the lesions with humans. In general, animal models of atherosclerosis are based on accelerated plaque formation due to a cholesterol-rich/Western-type diet, manipulation of genes involved in the cholesterol metabolism, and the introduction of additional risk factors for atherosclerosis...
May 5, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28475147/folic-acid-supplementation-delays-atherosclerotic-lesion-development-by-modulating-mcp1-and-vegf-dna-methylation-levels-in-vivo-and-in-vitro
#16
Shanshan Cui, Wen Li, Xin Lv, Pengyan Wang, Yuxia Gao, Guowei Huang
The pathogenesis of atherosclerosis has been partly acknowledged to result from aberrant epigenetic mechanisms. Accordingly, low folate levels are considered to be a contributing factor to promoting vascular disease because of deregulation of DNA methylation. We hypothesized that increasing the levels of folic acid may act via an epigenetic gene silencing mechanism to ameliorate atherosclerosis. Here, we investigated the atheroprotective effects of folic acid and the resultant methylation status in high-fat diet-fed ApoE knockout mice and in oxidized low-density lipoprotein-treated human umbilical vein endothelial cells...
May 5, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28473436/dba-2j-haplotype-on-distal-chromosome-2-reduces-mertk-expression-restricts-efferocytosis-and-increases-susceptibility-to-atherosclerosis
#17
Yukako Kayashima, Natalia Makhanova, Nobuyo Maeda
OBJECTIVE: Arch atherosclerosis 4 (Aath4) is a quantitative trait locus for atherosclerotic plaque formation in the inner curve of the aortic arch previously identified in an F2 cross of Apoe(-/-) mice on DBA/2J and 129S6 backgrounds. Mertk, coding for a ligand-activated transmembrane tyrosine kinase, is a candidate gene within the same chromosomal region. Our objective was to determine whether strain differences in Mertk influence plaque formation. APPROACH AND RESULTS: To dissect the strain effects of Mertk on atherosclerosis, we first established a congenic mouse line (Aath4a(DBA/DBA) ) in which a 5' region of Aath4 of DBA/2J, including Mertk, was backcrossed onto a 129S6-Apoe(-/-) background...
May 4, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28472596/reciprocal-regulation-between-mir-148a-152-and-dna-methyltransferase-1-is-associated-with-hyperhomocysteinemia-accelerated-atherosclerosis
#18
Anning Yang, Yue Sun, Yuan Gao, Songhao Yang, Caiyan Mao, Ning Ding, Mei Deng, Yanhua Wang, Xiaoling Yang, Yuexia Jia, Huiping Zhang, Yideng Jiang
DNA methyltransferase 1 (DNMT1) and miRNAs are both important regulators of gene expression that have been implicated in the pathogenesis of atherosclerosis. This study was designed to elucidate the potential interaction between DNMT1 and miRNAs in the context of hyperhomocysteinemia (HHcy)-related atherosclerosis. In the aorta of ApoE(-/-) mice fed a high methionine diet, increased expression of miR-148a/152, with decreased DNMT1 mRNA and protein levels, was detected. Similar changes were observed in cultured foam cells stimulated with homocysteine...
May 4, 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28465483/crispr-cas9-mediated-apoe-and-ldlr-double-gene-knockout-in-pigs-elevates-serum-ldl-c-and-tc-levels
#19
Lei Huang, Zaidong Hua, Hongwei Xiao, Ying Cheng, Kui Xu, Qian Gao, Ying Xia, Yang Liu, Xue Zhang, Xinming Zheng, Yulian Mu, Kui Li
The traditional method to establish a cardiovascular disease model induced by high fat and high cholesterol diets is time consuming and laborious and may not be appropriate in all circumstances. A suitable pig model to study metabolic disorders and subsequent atherosclerosis is not currently available. For this purpose, we applied the CRISPR/Cas9 system to Bama minipigs, targeting apolipoprotein E (ApoE) and low density lipoprotein receptor (LDLR) gene simultaneously. Six biallelic knockout pigs of these two genes were obtained successfully in a single step...
April 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28464262/a-tale-of-agriculturalists-and-hunter-gatherers-exploring-the-thrifty-genotype-hypothesis-in-native-south-americans
#20
Guillermo Reales, Diego L Rovaris, Vanessa C Jacovas, Tábita Hünemeier, José R Sandoval, Alcibiades Salazar-Granara, Darío A Demarchi, Eduardo Tarazona-Santos, Aline B Felkl, Michele A Serafini, Francisco M Salzano, Rafael Bisso-Machado, David Comas, Vanessa R Paixão-Côrtes, Maria Cátira Bortolini
OBJECTIVES: To determine genetic differences between agriculturalist and hunter-gatherer southern Native American populations for selected metabolism-related markers and to test whether Neel's thrifty genotype hypothesis (TGH) could explain the genetic patterns observed in these populations. MATERIALS AND METHODS: 375 Native South American individuals from 17 populations were genotyped using six markers (APOE rs429358 and rs7412; APOA2 rs5082; CD36 rs3211883; TCF7L2 rs11196205; and IGF2BP2 rs11705701)...
May 2, 2017: American Journal of Physical Anthropology
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