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Cardiovascular genomic

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https://www.readbyqxmd.com/read/29138211/transcriptome-sequencing-of-the-naked-mole-rat-heterocephalus-glaber-and-identification-of-hypoxia-tolerance-genes
#1
Bang Xiao, Li Li, Chang Xu, Shanmin Zhao, Lifang Lin, Jishuai Cheng, Wenjing Yang, Wei Cong, Guanghan Kan, Shufang Cui
The naked mole rat (NMR; Heterocephalus glaber) is a small rodent species found in regions of Kenya, Ethiopia and Somalia. It has a high tolerance for hypoxia and is thus, considered one of the most important natural models for studying hypoxia tolerance mechanisms. The various mechanisms underlying the NMR's hypoxia tolerance are beginning to be understood at different levels of organization, and next-generation sequencing methods promise to expand this understanding to the level of gene expression. In this study, we examined the sequence and transcript abundance data of the muscle transcriptome of NMRs exposed to hypoxia using the Illumina HiSeq 2500 system to clarify the possible genomic adaptive responses to the hypoxic underground surroundings...
November 14, 2017: Biology Open
https://www.readbyqxmd.com/read/29133894/microalbuminuria-as-a-simple-predictor-of-incident-diabetes-over-8-years-in-the-korean-genome-and-epidemiology-study-koges
#2
Dong-Hyuk Jung, Young-Sup Byun, Yu-Jin Kwon, Gwang-Sil Kim
Microalbuminuria (MAU) is a common subclinical disease and related with cardiovascular outcome both in diabetic and non-diabetic patients. However, there is rare data about the effect of MAU on the development of diabetes. Thus, we aimed to investigate whether MAU is associated with the development of incident diabetes. A total of 3385 subjects without diabetes (1503 men and 1882 women; mean age, 53 years) who participated in the Ansung-Ansan cohort study from 2001-2002 (baseline) to 2011-2012 (fifth follow-up visit) were followed for a mean of 8 years...
November 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29130076/crispr-correction-of-a-homozygous-low-density-lipoprotein-receptor-mutation-in-familial-hypercholesterolemia-induced-pluripotent-stem-cells
#3
Linda Omer, Elizabeth A Hudson, Shirong Zheng, James B Hoying, Yuan Shan, Nolan L Boyd
Familial hypercholesterolemia (FH) is a hereditary disease primarily due to mutations in the low-density lipoprotein receptor (LDLR) that lead to elevated cholesterol and premature development of cardiovascular disease. Homozygous FH patients (HoFH) with two dysfunctional LDLR alleles are not as successfully treated with standard hypercholesterol therapies, and more aggressive therapeutic approaches to control cholesterol levels must be considered. Liver transplant can resolve HoFH, and hepatocyte transplantation has shown promising results in animals and humans...
November 2017: Hepatol Commun
https://www.readbyqxmd.com/read/29127183/genome-wide-association-study-of-pr-interval-in-hispanics-latinos-identifies-novel-locus-at-id2
#4
Amanda A Seyerle, Henry J Lin, Stephanie M Gogarten, Adrienne Stilp, Raul Méndez Giráldez, Elsayed Soliman, Antoine Baldassari, Mariaelisa Graff, Susan Heckbert, Kathleen F Kerr, Charles Kooperberg, Carlos Rodriguez, Xiuqing Guo, Jie Yao, Nona Sotoodehnia, Kent D Taylor, Eric A Whitsel, Jerome I Rotter, Cathy C Laurie, Christy Avery
OBJECTIVE: PR interval (PR) is a heritable electrocardiographic measure of atrial and atrioventricular nodal conduction. Changes in PR duration may be associated with atrial fibrillation, heart failure and all-cause mortality. Hispanic/Latino populations have high burdens of cardiovascular morbidity and mortality, are highly admixed and represent exceptional opportunities for novel locus identification. However, they remain chronically understudied. We present the first genome-wide association study (GWAS) of PR in 14 756 participants of Hispanic/Latino ancestry from three studies...
November 10, 2017: Heart: Official Journal of the British Cardiac Society
https://www.readbyqxmd.com/read/29121093/fish-oil-omega-3-polyunsaturated-fatty-acids-attenuate-oxidative-stress-induced-dna-damage-in-vascular-endothelial-cells
#5
Chiemi Sakai, Mari Ishida, Hideo Ohba, Hiromitsu Yamashita, Hitomi Uchida, Masao Yoshizumi, Takafumi Ishida
OBJECTIVE: Omega-3 fatty acids, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), likely prevent cardiovascular disease, however their mechanisms remain unclear. Recently, the role of DNA damage in atherogenesis has been receiving considerable attention. Here, we investigated the effects of EPA and DHA on DNA damage in vascular endothelial cells to clarify their antiatherogenic mechanisms. METHODS AND RESULTS: We determined the effect of EPA and DHA on H2O2-induced DNA damage response in human aortic endothelial cells...
2017: PloS One
https://www.readbyqxmd.com/read/29112599/genetic-variants-associated-with-earlier-age-at-menopause-increase-the-risk-of-cardiovascular-events-in-women
#6
Chloé Sarnowski, Maryam Kavousi, Steve Isaacs, Ellen W Demerath, Linda Broer, Taulant Muka, Oscar H Franco, Mohammad Arfan Ikram, André Uitterlinden, Nora Franceschini, Kathryn L Lunetta, Joanne M Murabito
OBJECTIVE: To better understand the relationship between cardiovascular disease risk and age-at-natural menopause using genetic data. METHODS: Early menopause is associated with cardiovascular disease risk. We constructed a genetic risk score comprising 56 age-at-natural menopause decreasing alleles in men and women from the Framingham Heart Study, the Atherosclerosis Risk in Communities Study, and the Rotterdam Study. If the genetic predisposition to earlier age-at-natural menopause is associated with increased cardiovascular disease risk, it is reasonable to ask whether the risk is shared by men carrying the alleles, despite not experiencing menopause...
November 6, 2017: Menopause: the Journal of the North American Menopause Society
https://www.readbyqxmd.com/read/29112333/associations-of-activated-coagulation-factor-vii-and-factor-viia-antithrombin-levels-with-genome-wide-polymorphisms-and-cardiovascular-disease-risk
#7
N C Olson, L M Raffield, L A Lange, E M Lange, W T Longstreth, G Chauhan, S Debette, S Seshadri, A P Reiner, R P Tracy
BACKGROUND: A fraction of coagulation factor VII circulates as an active protease (FVIIa). FVIIa also circulates as an inactivated complex with antithrombin (FVIIa-AT). OBJECTIVE: Evaluate associations of FVIIa and FVIIa-AT with genome-wide single nucleotide polymorphisms (SNPs) and incident coronary heart disease, ischemic stroke, and mortality. PATIENTS/METHODS: We measured FVIIa and FVIIa-AT in 3,486 Cardiovascular Health Study (CHS) participants...
November 7, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/29110756/apol1-nephropathy-a-population-genetics-and-evolutionary-medicine-detective-story
#8
REVIEW
Etty Kruzel-Davila, Walter G Wasser, Karl Skorecki
Common DNA sequence variants rarely have a high-risk association with a common disease. When such associations do occur, evolutionary forces must be sought, such as in the association of apolipoprotein L1 (APOL1) gene risk variants with nondiabetic kidney diseases in populations of African ancestry. The variants originated in West Africa and provided pathogenic resistance in the heterozygous state that led to high allele frequencies owing to an adaptive evolutionary selective sweep. However, the homozygous state is disadvantageous and is associated with a markedly increased risk of a spectrum of kidney diseases encompassing hypertension-attributed kidney disease, focal segmental glomerulosclerosis, human immunodeficiency virus nephropathy, sickle cell nephropathy, and progressive lupus nephritis...
November 2017: Seminars in Nephrology
https://www.readbyqxmd.com/read/29104511/atp2b1-gene-silencing-increases-insulin-sensitivity-through-facilitating-akt-activation-via-the-ca-2-calmodulin-signaling-pathway-and-ca-2-associated-enos-activation-in-endothelial-cells
#9
Yang Long, Ji-Yi Xia, Shao-Wei Chen, Chen-Lin Gao, Guan-Nan Liang, Xue-Mei He, Jian Wu, Chun-Xia Jiang, Xin Liu, Wei Huang, Qin Wan, Yong Xu
Endothelial cell insulin resistance may be partially responsible for the higher risk of atherosclerosis and cardiovascular disease in populations with insulin resistance and type 2 diabetes mellitus (T2DM). A genome-wide association study revealed a significant association between the ATPase plasma membrane Ca(2+) transporting 1 (ATP2B1) gene and T2DM in two community-based cohorts from the Korea Association Resource Project. However, little is known about the implication of the ATP2B1 gene on T2DM. In the present study, we investigated the role of the ATP2B1 gene in endothelial cell insulin sensitivity...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/29100088/natural-selection-on-genes-related-to-cardiovascular-health-in-high-altitude-adapted-andeans
#10
Jacob E Crawford, Ricardo Amaru, Jihyun Song, Colleen G Julian, Fernando Racimo, Jade Yu Cheng, Xiuqing Guo, Jie Yao, Bharath Ambale-Venkatesh, João A Lima, Jerome I Rotter, Josef Stehlik, Lorna G Moore, Josef T Prchal, Rasmus Nielsen
The increase in red blood cell mass (polycythemia) due to the reduced oxygen availability (hypoxia) of residence at high altitude or other conditions is generally thought to be beneficial in terms of increasing tissue oxygen supply. However, the extreme polycythemia and accompanying increased mortality due to heart failure in chronic mountain sickness most likely reduces fitness. Tibetan highlanders have adapted to high altitude, possibly in part via the selection of genetic variants associated with reduced polycythemic response to hypoxia...
November 2, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/29098321/sugar-sweetened-beverage-intake-associations-with-fasting-glucose-and-insulin-concentrations-are-not-modified-by-selected-genetic-variants-in-a-chrebp-fgf21-pathway-a-meta-analysis
#11
Nicola M McKeown, Hassan S Dashti, Jiantao Ma, Danielle E Haslam, Jessica C Kiefte-de Jong, Caren E Smith, Toshiko Tanaka, Mariaelisa Graff, Rozenn N Lemaitre, Denis Rybin, Emily Sonestedt, Alexis C Frazier-Wood, Dennis O Mook-Kanamori, Yanping Li, Carol A Wang, Elisabeth T M Leermakers, Vera Mikkilä, Kristin L Young, Kenneth J Mukamal, L Adrienne Cupples, Christina-Alexandra Schulz, Tzu-An Chen, Ruifang Li-Gao, Tao Huang, Wendy H Oddy, Olli Raitakari, Kenneth Rice, James B Meigs, Ulrika Ericson, Lyn M Steffen, Frits R Rosendaal, Albert Hofman, Mika Kähönen, Bruce M Psaty, Louise Brunkwall, Andre G Uitterlinden, Jorma Viikari, David S Siscovick, Ilkka Seppälä, Kari E North, Dariush Mozaffarian, Josée Dupuis, Marju Orho-Melander, Stephen S Rich, Renée de Mutsert, Lu Qi, Craig E Pennell, Oscar H Franco, Terho Lehtimäki, Mark A Herman
AIMS/HYPOTHESIS: Sugar-sweetened beverages (SSBs) are a major dietary contributor to fructose intake. A molecular pathway involving the carbohydrate responsive element-binding protein (ChREBP) and the metabolic hormone fibroblast growth factor 21 (FGF21) may influence sugar metabolism and, thereby, contribute to fructose-induced metabolic disease. We hypothesise that common variants in 11 genes involved in fructose metabolism and the ChREBP-FGF21 pathway may interact with SSB intake to exacerbate positive associations between higher SSB intake and glycaemic traits...
November 2, 2017: Diabetologia
https://www.readbyqxmd.com/read/29097610/understanding-mitochondrial-polymorphisms-in-cancer
#12
REVIEW
Karen M Bussard, Linda D Siracusa
Alterations in mitochondrial DNA (mtDNA) were once thought to be predominantly innocuous to cell growth. Recent evidence suggests that mtDNA undergo naturally occurring alterations, including mutations and polymorphisms, which profoundly affect the cells in which they appear and contribute to a variety of diseases, including cardiovascular disease, diabetes, and cancer. Furthermore, interplay between mtDNA and nuclear DNA has been found in cancer cells, necessitating consideration of these complex interactions for future studies of cancer mutations and polymorphisms...
November 2, 2017: Cancer Research
https://www.readbyqxmd.com/read/29096998/a-deep-phenotype-association-study-reveals-specific-phenotype-associations-with-genetic-variants-in-age-related-macular-degeneration-age-related-eye-disease-study-2-areds2-report-no-14
#13
Freekje van Asten, Michael Simmons, Ayush Singhal, Tiarnan D Keenan, Rinki Ratnapriya, Elvira Agrón, Traci E Clemons, Anand Swaroop, Zhiyong Lu, Emily Y Chew
PURPOSE: Age-related macular degeneration (AMD), a multifactorial disease with variable phenotypic presentation, was associated with 52 single nucleotide polymorphisms (SNPs) at 34 loci in a genome-wide association study (GWAS). These genetic variants could modulate different biological pathways involved in AMD, contributing to phenotypic variability. To better understand the effects of these SNPs, we performed a deep phenotype association study (DeePAS) in the Age-Related Eye Disease Study 2 (AREDS2), followed by replication using AREDS participants, to identify genotype associations with AMD and non-AMD ocular and systemic phenotypes...
October 30, 2017: Ophthalmology
https://www.readbyqxmd.com/read/29094207/peripheral-arterial-disease-genetics-progress-to-date-and-challenges-ahead
#14
REVIEW
Nathan Belkin, Scott M Damrauer
PURPOSE OF REVIEW: In this paper, we review the progress made thus far in research related to the genetics of peripheral arterial disease (PAD) by detailing efforts to date in heritability, linkage analyses, and candidate gene studies. We further summarize more contemporary genome-wide association studies (GWAS) and epigenetic studies of PAD. Finally, we review current challenges and future avenues of advanced research in PAD genetics including whole genome sequencing studies. RECENT FINDINGS: Studies have estimated the heritability of PAD to be moderate, though the contribution to this heritability that is independent of traditional cardiovascular risk factors remains unclear...
November 1, 2017: Current Cardiology Reports
https://www.readbyqxmd.com/read/29089340/genetic-variation-at-the-adamts7-locus-is-associated-with-reduced-severity-of-coronary-artery-disease
#15
Kenneth Chan, Xiangyuan Pu, Pratik Sandesara, Robin N Poston, Iain A Simpson, Arshed A Quyyumi, Shu Ye, Riyaz S Patel
BACKGROUND: Genome-wide association studies identified ADAMTS7 as a risk locus for coronary artery disease (CAD). Functional studies suggest that ADAMTS7 may promote cellular processes in atherosclerosis. We sought to examine the association between genetic variation at ADAMTS7 and measures of atherosclerosis using histological, angiographic, and clinical outcomes data. METHODS AND RESULTS: The lead CAD-associated single-nucleotide polymorphism rs3825807 at the ADAMTS7 locus was genotyped...
October 31, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29084231/common-low-frequency-and-rare-genetic-variants-associated-with-lipoprotein-subclasses-and-triglyceride-measures-in-finnish-men-from-the-metsim-study
#16
James P Davis, Jeroen R Huyghe, Adam E Locke, Anne U Jackson, Xueling Sim, Heather M Stringham, Tanya M Teslovich, Ryan P Welch, Christian Fuchsberger, Narisu Narisu, Peter S Chines, Antti J Kangas, Pasi Soininen, Mika Ala-Korpela, Johanna Kuusisto, Francis S Collins, Markku Laakso, Michael Boehnke, Karen L Mohlke
Lipid and lipoprotein subclasses are associated with metabolic and cardiovascular diseases, yet the genetic contributions to variability in subclass traits are not fully understood. We conducted single-variant and gene-based association tests between 15.1M variants from genome-wide and exome array and imputed genotypes and 72 lipid and lipoprotein traits in 8,372 Finns. After accounting for 885 variants at 157 previously identified lipid loci, we identified five novel signals near established loci at HIF3A, ADAMTS3, PLTP, LCAT, and LIPG...
October 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29069341/epigenetics-and-precision-medicine-in-cardiovascular-patients-from-basic-concepts-to-the-clinical-arena
#17
Sarah Costantino, Peter Libby, Raj Kishore, Jean-Claude Tardif, Assam El-Osta, Francesco Paneni
Cardiovascular diseases (CVDs) remain the leading cause of mortality worldwide and also inflict major burdens on morbidity, quality of life, and societal costs. Considering that CVD preventive medications improve vascular outcomes in less than half of patients (often relative risk reductions range from 12% to 20% compared with placebo), precision medicine offers an attractive approach to refine the targeting of CVD medications to responsive individuals in a population and thus allocate resources more wisely and effectively...
October 23, 2017: European Heart Journal
https://www.readbyqxmd.com/read/29067024/multifaceted-role-of-neuropilins-in-the-immune-system-potential-targets-for-immunotherapy
#18
REVIEW
Sohini Roy, Arup K Bag, Rakesh K Singh, James E Talmadge, Surinder K Batra, Kaustubh Datta
Neuropilins (NRPs) are non-tyrosine kinase cell surface glycoproteins expressed in all vertebrates and widely conserved across species. The two isoforms, such as neuropilin-1 (NRP1) and neuropilin-2 (NRP2), mainly act as coreceptors for class III Semaphorins and for members of the vascular endothelial growth factor family of molecules and are widely known for their role in a wide array of physiological processes, such as cardiovascular, neuronal development and patterning, angiogenesis, lymphangiogenesis, as well as various clinical disorders...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29065927/the-protective-role-of-estrogen-and-estrogen-receptors-in-cardiovascular-disease-and-the-controversial-use-of-estrogen-therapy
#19
REVIEW
Andrea Iorga, Christine M Cunningham, Shayan Moazeni, Gregoire Ruffenach, Soban Umar, Mansoureh Eghbali
Epidemiologic studies have previously suggested that premenopausal females have reduced incidence of cardiovascular disease (CVD) when compared to age-matched males, and the incidence and severity of CVD increases postmenopause. The lower incidence of cardiovascular disease in women during reproductive age is attributed at least in part to estrogen (E2). E2 binds to the traditional E2 receptors (ERs), estrogen receptor alpha (ERα), and estrogen receptor beta (ERβ), as well as the more recently identified G-protein-coupled ER (GPR30), and can exert both genomic and non-genomic actions...
October 24, 2017: Biology of Sex Differences
https://www.readbyqxmd.com/read/29065852/genetic-determinants-of-growth-hormone-and-gh-related-phenotypes
#20
Erik Hallengren, Peter Almgren, Malin Svensson, Widet Gallo, Gunnar Engström, Margaretha Persson, Olle Melander
BACKGROUND: Higher fasting Growth Hormone (GH) has been associated with increased cardiovascular morbidity and mortality. Our objective was to find genetic determinants of fasting GH in order to facilitate future efforts of analyzing the association between fasting growth hormone and cardiovascular disease. A genome-wide association study (GWAS) was performed in a discovery cohort of 4134 persons (58% females; age 46-68 yrs), linking SNPs to fasting hs-GH. Fifteen SNPs were replicated in an independent cohort of 5262 persons (28...
October 24, 2017: BMC Genomics
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