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Adcy9

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https://www.readbyqxmd.com/read/29739919/identification-of-core-genes-and-key-pathways-via-integrated-analysis-of-gene-expression-and-dna-methylation-profiles-in-bladder-cancer
#1
Yongzhen Zhang, Liang Fang, Yuanwei Zang, Zhonghua Xu
BACKGROUND Bladder cancer (BC) is the most common urological malignant tumor. In BC, aberrant DNA methylation is believed to be associated with carcinogenesis. Therefore, the identification of key genes and pathways could help determine the potential molecular mechanisms of BC development. MATERIAL AND METHODS Microarray data on gene expression and gene methylation were downloaded from the Gene Expression Omnibus (GEO) database. Abnormal methylated/expressed genes were analyzed by GEO2R and statistical software R...
May 9, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29674325/adenylate-cyclase-type-9-adcy9-inactivation-protects-from-atherosclerosis-only-in-the-absence-of-cholesteryl-ester-transfer-protein-cetp
#2
Yohann Rautureau, Vanessa Deschambault, Marie-Ève Higgins, Daniel Rivas, Mélanie Mecteau, Pascale Geoffroy, Géraldine Miquel, Kurunradeth Uy, Rocio Sanchez, Véronique Lavoie, Geneviève Brand, Audrey Nault, Pierre-Marc Williams, Maria Laura Suarez, Nolwenn Merlet, Line Lapointe, Natacha Duquette, Marc-Antoine Gillis, Samaneh Samami, Gaétan Mayer, Philippe Pouliot, Adeline Raignault, Foued Maafi, Mathieu R Brodeur, Sylvie Levesque, Marie-Claude Guertin, Marie-Pierre Dubé, Éric Thorin, David Rhainds, Éric Rhéaume, Jean-Claude Tardif
Background -Pharmacogenomic studies have shown that ADCY9 genotype determines the effects of the cholesteryl ester transfer protein (CETP) inhibitor dalcetrapib on cardiovascular events and atherosclerosis imaging. The underlying mechanisms responsible for the interactions between ADCY9 and CETP activity have not yet been determined. Methods - Adcy9 -inactivated ( Adcy9 Gt/Gt ) and wild-type (WT) mice, that were or not transgenic for the CETP gene (CETPtg Adcy9 Gt/Gt and CETPtg Adcy9 WT ), were submitted to an atherogenic protocol (injection of an AAV8 expressing a PCSK9 gain-of-function variant and 0...
April 19, 2018: Circulation
https://www.readbyqxmd.com/read/29525816/adcy9-genetic-variants-and-cardiovascular-outcomes-with-evacetrapib-in-patients-with-high-risk-vascular-disease-a-nested-case-control-study
#3
Steven E Nissen, Sreekumar G Pillai, Stephen J Nicholls, Kathy Wolski, Jeffrey S Riesmeyer, Govinda J Weerakkody, Wendra M Foster, Ellen McErlean, Lin Li, Pallav Bhatnagar, Giacomo Ruotolo, A Michael Lincoff
Importance: A pharmacogenetic analysis of dalcetrapib, a cholesteryl ester transfer protein inhibitor, reported an association between a single-nucleotide polymorphism (SNP) in the ADCY9 gene (rs1967309) and reduction in major adverse cardiovascular events despite a neutral result for the overall trial. Objective: To determine whether the association between the SNP in the ADCY9 gene and a reduction in major adverse cardiovascular events could be replicated for another cholesteryl ester transfer protein inhibitor, evacetrapib, in patients with high-risk vascular disease...
March 11, 2018: JAMA Cardiology
https://www.readbyqxmd.com/read/29515040/a-peripheral-blood-transcriptomic-signature-predicts-autoantibody-development-in-infants-at-risk-of-type-1-diabetes
#4
Ahmed M Mehdi, Emma E Hamilton-Williams, Alexandre Cristino, Anette Ziegler, Ezio Bonifacio, Kim-Anh Le Cao, Mark Harris, Ranjeny Thomas
Autoimmune-mediated destruction of pancreatic islet β cells results in type 1 diabetes (T1D). Serum islet autoantibodies usually develop in genetically susceptible individuals in early childhood before T1D onset, with multiple islet autoantibodies predicting diabetes development. However, most at-risk children remain islet-antibody negative, and no test currently identifies those likely to seroconvert. We sought a genomic signature predicting seroconversion risk by integrating longitudinal peripheral blood gene expression profiles collected in high-risk children included in the BABYDIET and DIPP cohorts, of whom 50 seroconverted...
March 8, 2018: JCI Insight
https://www.readbyqxmd.com/read/29324442/the-epithelial-to-mesenchymal-transition-activator-zeb1-initiates-a-prometastatic-competing-endogenous-rna-network
#5
Xiaochao Tan, Priyam Banerjee, Xin Liu, Jiang Yu, Don L Gibbons, Ping Wu, Kenneth L Scott, Lixia Diao, Xiaofeng Zheng, Jing Wang, Ali Jalali, Milind Suraokar, Junya Fujimoto, Carmen Behrens, Xiuping Liu, Chang-Gong Liu, Chad J Creighton, Ignacio I Wistuba, Jonathan M Kurie
Epithelial tumor cells undergo epithelial-to-mesenchymal transition (EMT) to gain metastatic activity. Competing endogenous RNAs (ceRNAs) have binding sites for a common set of microRNAs (miRs) and regulate each other's expression by sponging miRs. Here, we address whether ceRNAs govern metastasis driven by the EMT-activating transcription factor ZEB1. High miR-181b levels were correlated with an improved prognosis in human lung adenocarcinomas, and metastatic tumor cell lines derived from a murine lung adenocarcinoma model in which metastasis is ZEB1-driven were enriched in miR-181b targets...
April 2, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29180230/glucocorticoids-genes-and-brain-function
#6
REVIEW
Grzegorz R Juszczak, Adrian M Stankiewicz
The identification of key genes in transcriptomic data constitutes a huge challenge. Our review of microarray reports revealed 88 genes whose transcription is consistently regulated by glucocorticoids (GCs), such as cortisol, corticosterone and dexamethasone, in the brain. Replicable transcriptomic data were combined with biochemical and physiological data to create an integrated view of the effects induced by GCs. The most frequently reported genes were Errfi1 and Ddit4. Their up-regulation was associated with the altered transcription of genes regulating growth factor and mTORC1 signaling (Gab1, Tsc22d3, Dusp1, Ndrg2, Ppp5c and Sesn1) and progression of the cell cycle (Ccnd1, Cdkn1a and Cables1)...
March 2, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28792790/recent-developments-and-future-directions-for-the-use-of-pharmacogenomics-in-cardiovascular-disease-treatments
#7
REVIEW
Elliot Berinstein, Andrew Levy
Cardiovascular disease is still the leading cause of death worldwide. There are many environmental and genetic factors that play a role in the development of cardiovascular disease. The treatment of cardiovascular disease is beginning to move in the direction of personalized medicine by using biomarkers from the patient's genome to design more effective treatment plans. Pharmacogenomics have already uncovered many links between genetic variation and response of many different drugs. Areas covered: This article will focus on the main polymorphisms that impact the risk of adverse effects and response efficacy of statins, clopidogrel, aspirin, β-blockers, warfarin dalcetrapib and vitamin E...
September 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28412787/-progress-in-studies-on-the-genetic-risk-factors-for-nonsyndromic-cleft-lip-or-palate-in-china
#8
Y Q Huang
Cleft lip and palate is the most common congenital defects of oral and maxillofacial region in human beings. The etiology of this malformation is complex, with both genetic and environmental causal factors are involved. To provide a better understanding in the genetic etiology of cleft lip or palate, the author summarized recent years studies based on Chinese population. Those researches included validation of some candidate genes for cleft lip or palate, using genome wide association analysis which included six independent cohorts from China to elucidate the genetic architecture of non-syndromic cleft lip with or without cleft palate in Chinese population and finally found a new susceptibility locus...
April 9, 2017: Zhonghua Kou Qiang Yi Xue za Zhi, Zhonghua Kouqiang Yixue Zazhi, Chinese Journal of Stomatology
https://www.readbyqxmd.com/read/28402597/gene-gene-interaction-of-single-nucleotide-polymorphisms-in-16p13-3-may-contribute-to-the-risk-of-non-syndromic-cleft-lip-with-or-without-cleft-palate-in-chinese-case-parent-trios
#9
Dongjing Liu, Hong Wang, Holger Schwender, Mary L Marazita, Zhuqing Wang, Yuan Yuan, Ping Wang, Kung Yee Liang, Yah Huei Wu-Chou, Mengying Wang, Bing Shi, Hongping Zhu, Tao Wu, Terri H Beaty
Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a common birth defect with a complex and heterogeneous etiology. A recent genome-wide association study (GWAS) among Chinese populations has identified a new region at 16p13.3 as being associated with NSCL/P, which requires further replication. Here, we attempted to replicate and further clarify the genetic association between this region and NSCL/P, as well as testing for potential gene-gene (G × G) and gene-environment (G × E) interactions...
June 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28193157/whole-genome-association-analysis-of-pork-meat-ph-revealed-three-significant-regions-and-several-potential-genes-in-finnish-yorkshire-pigs
#10
Lucas L Verardo, Marja-Liisa Sevón-Aimonen, Timo Serenius, Ville Hietakangas, Pekka Uimari
BACKGROUND: One of the most commonly used quality measurements of pork is pH measured 24 h after slaughter. The most probable mode of inheritance for this trait is oligogenic with several known major genes, such as PRKAG3. In this study, we used whole-genome SNP genotypes of over 700 AI boars; after a quality check, 42,385 SNPs remained for association analysis. All the boars were purebred Finnish Yorkshire. To account for relatedness of the animals, a pedigree-based relationship matrix was used in a mixed linear model to test the effect of SNPs on pH measured from loin...
February 13, 2017: BMC Genetics
https://www.readbyqxmd.com/read/28126828/cetp-pharmacogenomics-based-response-to-the-cetp-inhibitor-dalcetrapib
#11
Jean-Claude Tardif, David Rhainds, Eric Rhéaume, Marie-Pierre Dubé
High-density lipoproteins are involved in reverse cholesterol transport and possess anti-inflammatory and antioxidative properties. Paradoxically, CETP (cholesteryl ester transfer protein) inhibitors have been shown to increase inflammation as revealed by a raised plasma level of high-sensitivity C-reactive protein. CETP inhibitors did not improve clinical outcomes in large-scale clinical trials of unselected patients with coronary disease. Dalcetrapib is a CETP modulator for which effects on cardiovascular outcomes were demonstrated in the dal-OUTCOMES trial to be influenced by correlated polymorphisms in the ADCY9 (adenylate cyclase type 9) gene (P=2...
March 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28076799/adenylyl-cyclase-type-9-gene-polymorphisms-are-associated-with-asthma-and-allergy-in-brazilian-children
#12
Helena M P Teixeira, Neuza M Alcantara-Neves, Maurício Barreto, Camila A Figueiredo, Ryan S Costa
Asthma is a chronic inflammatory disease of the respiratory tract. This heterogeneous disease is caused by the interaction of interindividual genetic variability and environmental factors. The gene adenylyl cyclase type 9 (ADCY9) encodes a protein called adenylyl cyclase (AC), responsible for producing the second messenger cyclic AMP (cAMP). cAMP is produced by T regulatory cells and is involved in the down-regulation of T effector cells. Failures in cAMP production may be related to an imbalance in the regulatory immune response, leading to immune-mediated diseases, such as allergic disorders...
February 2017: Molecular Immunology
https://www.readbyqxmd.com/read/27915366/aging-has-the-opposite-effect-on-camp-and-cgmp-circadian-variations-in-rat-leydig-cells
#13
Aleksandar Z Baburski, Srdjan J Sokanovic, Silvana A Andric, Tatjana S Kostic
The Leydig cell physiology displays a circadian rhythm driven by a complex interaction of the reproductive axis hormones and circadian system. The final output of this regulatory process is circadian pattern of steroidogenic genes expression and testosterone production. Aging gradually decreases robustness of rhythmic testosterone secretion without change in pattern of LH secretion. Here, we analyzed effect of aging on circadian variation of cAMP and cGMP signaling in Leydig cells. Results showed opposite effect of aging on cAMP and cGMP daily variation...
May 2017: Journal of Comparative Physiology. B, Biochemical, Systemic, and Environmental Physiology
https://www.readbyqxmd.com/read/27900865/-treatment-of-dyslipidemia-is-here-still-place-for-cetp-inhibitors
#14
Ján Murín, Miroslav Pernický, Soňa Kiňová
In the treatment of dyslipidemias about 5-6 years back a new class of drugs emerged, CETP (cholesteryl ester transfer protein)-inhibitors. Their benefit was due to an increase of HDL-cholesterol (HDL-C) serum levels. This treatment mode was supported by epidemiological and clinical studies, as people with high serum HDL-C levels suffered less from cardiovascular (CV) events. Three studies with CETP inhibitors (ILLUMINATE with torcetrapib, dal-OUTCOMES with dalcetrapib and ACCELERATE with evacetrapib) were unfortunately negative, and torcetrapib was even harmful to patients due to an increase of aldosterone serum levels...
December 0: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/27734840/genetic-polymorphism-of-nonsyndromic-cleft-lip-with-or-without-cleft-palate-is-associated-with-developmental-dyslexia-in-chinese-school-aged-populations
#15
Bin Wang, Yuxi Zhou, Song Leng, Liyuan Zheng, Hong Lv, Fei Wang, Li-Hai Tan, Yimin Sun
Developmental dyslexia (DD) is a neurodevelopment disorder characterized by reading disabilities without apparent etiologies. Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is a structural craniofacial malformation featured by isolated orofacial abnormalities. Despite substantial phenotypic differences, potential linkage between these two disorders has been suggested as prevalence of DD among NSCL/P patients was much higher than that in general populations. Previous neuroimaging studies observed impaired short-term memory in patients with DD and NSCL/P, respectively...
February 2017: Journal of Human Genetics
https://www.readbyqxmd.com/read/27676198/pharmacogenomic-approaches-to-lipid-regulating-trials
#16
REVIEW
Marie-Jeanne Bertrand, Marie-Pierre Dubé, Jean-Claude Tardif
PURPOSE OF REVIEW: Randomized clinical outcome trials are costly, long, and often yield neutral or modestly positive results, and these issues have impeded cardiovascular drug development in the past decade. Despite the significant reduction of cardiovascular morbidity and mortality with statins, substantial residual risk of major cardiovascular events remains. This could be because of the difficulty of demonstrating benefits of new drugs in addition to the current standard of care in unselected populations as well as the interindividual variability in drug response...
December 2016: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/27500488/recurrent-ezh1-mutations-are-a-second-hit-in-autonomous-thyroid-adenomas
#17
Davide Calebiro, Elisa S Grassi, Markus Eszlinger, Cristina L Ronchi, Amod Godbole, Kerstin Bathon, Fabiana Guizzardi, Tiziana de Filippis, Knut Krohn, Holger Jaeschke, Thomas Schwarzmayr, Rifat Bircan, Hulya Iliksu Gozu, Seda Sancak, Marek Niedziela, Tim M Strom, Martin Fassnacht, Luca Persani, Ralf Paschke
Autonomous thyroid adenomas (ATAs) are a frequent cause of hyperthyroidism. Mutations in the genes encoding the TSH receptor (TSHR) or the Gs protein α subunit (GNAS) are found in approximately 70% of ATAs. The involvement of other genes and the pathogenesis of the remaining cases are presently unknown. Here, we performed whole-exome sequencing in 19 ATAs that were paired with normal DNA samples and identified a recurrent hot-spot mutation (c.1712A>G; p.Gln571Arg) in the enhancer of zeste homolog 1 (EZH1) gene, which codes for a catalytic subunit of the polycomb complex...
September 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27477082/genome-wide-dna-methylation-pattern-in-visceral-adipose-tissue-differentiates-insulin-resistant-from-insulin-sensitive-obese-subjects
#18
A B Crujeiras, A Diaz-Lagares, J M Moreno-Navarrete, J Sandoval, D Hervas, A Gomez, W Ricart, F F Casanueva, M Esteller, J M Fernandez-Real
Elucidating the potential mechanisms involved in the detrimental effect of excess body weight on insulin action is an important priority in counteracting obesity-associated diseases. The present study aimed to disentangle the epigenetic basis of insulin resistance by performing a genome-wide epigenetic analysis in visceral adipose tissue (VAT) from morbidly obese patients depending on the insulin sensitivity evaluated by the clamp technique. The global human methylome screening performed in VAT from 7 insulin-resistant (IR) and 5 insulin-sensitive (IS) morbidly obese patients (discovery cohort) analyzed using the Infinium HumanMethylation450 BeadChip array identified 982 CpG sites able to perfectly separate the IR and IS samples...
December 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/27418594/genotype-dependent-effects-of-dalcetrapib-on-cholesterol-efflux-and-inflammation-concordance-with-clinical-outcomes
#19
RANDOMIZED CONTROLLED TRIAL
Jean-Claude Tardif, David Rhainds, Mathieu Brodeur, Yassamin Feroz Zada, René Fouodjio, Sylvie Provost, Marie Boulé, Sonia Alem, Jean C Grégoire, Philippe L L'Allier, Reda Ibrahim, Marie-Claude Guertin, Ian Mongrain, Anders G Olsson, Gregory G Schwartz, Eric Rhéaume, Marie-Pierre Dubé
BACKGROUND: Dalcetrapib effects on cardiovascular outcomes are determined by adenylate cyclase 9 gene polymorphisms. Our aim was to determine whether these clinical end point results are also associated with changes in reverse cholesterol transport and inflammation. METHODS AND RESULTS: Participants of the dal-OUTCOMES and dal-PLAQUE-2 trials were randomly assigned to receive dalcetrapib or placebo in addition to standard care. High-sensitivity C-reactive protein was measured at baseline and at end of study in 5243 patients from dal-OUTCOMES also genotyped for the rs1967309 polymorphism in adenylate cyclase 9...
August 2016: Circulation. Cardiovascular Genetics
https://www.readbyqxmd.com/read/26854454/genome-wide-pathway-analysis-in-pancreatic-cancer
#20
Young Ho Lee, Gwan Gyu Song
PURPOSE: The purpose of this study was to identify candidate single-nucleotide polymorphisms (SNPs) that might play a role in susceptibility to pancreatic cancer, elucidate their potential mechanisms, and generate SNP-to-gene-to-pathway hypotheses. METHODS: A genome-wide association study (GWAS) dataset of pancreatic cancer that included 496,959 SNPs from 3,851 pancreatic cancer patients and 3,934 control subjects of European descent was used in this study. The Identify candidate Causal SNPs and Pathways (ICSNPathway) method was applied to the GWAS dataset...
November 2015: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
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