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https://www.readbyqxmd.com/read/28220878/homozygous-carriers-of-the-tcf7l2-rs7903146-t-allele-show-altered-postprandial-response-in-triglycerides-and-triglyceride-rich-lipoproteins
#1
L Engelbrechtsen, T H Hansen, Y Mahendran, P Pyl, E Andersson, A Jonsson, A Gjesing, A Linneberg, T Jørgensen, T Hansen, H Vestergaard
The TCF7L2 rs7903146 T-allele shows the strongest association with type 2 diabetes (T2D) among common gene variants. The aim of this study was to assess circulating levels of metabolites following a meal test in individuals carrying the high risk rs790346 TT genotype (cases) and low-risk CC genotype (controls). Sixty-two men were recruited based on TCF7L2 genotype, 31 were TT carriers and 31 were age- and BMI-matched CC carriers. All participants consumed a test meal after 12 hours of fasting. Metabolites were measured using proton nuclear magnetic resonance (NMR) spectroscopy...
February 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28219951/generation-of-thalamic-neurons-from-mouse-embryonic-stem-cells
#2
Atsushi Shiraishi, Keiko Muguruma, Yoshiki Sasai
Thalamus is a diencephalic structure that plays crucial roles in relaying and modulating sensory and motor information to the neocortex. The thalamus develops in the dorsal part of the neural tube at the level of the caudal forebrain. However, the molecular mechanisms that are essential for thalamic differentiation are still unknown. Here we have succeeded in the generation of thalamic neurons from mouse ES cells (mESCs) by modifying the default method that induces the most-anterior neural type in self-organizing culture...
February 20, 2017: Development
https://www.readbyqxmd.com/read/28219675/tcf7l2-plays-crucial-roles-in-forebrain-development-through-regulation-of-thalamic-and-habenular-neuron-identity-and-connectivity
#3
Myungsin Lee, Jiyeon Yoon, Hobeom Song, Bumwhee Lee, Lam Tri Duc, Jaeseung Yoon, Kwanghee Baek, Hans Clevers, Yongsu Jeong
The thalamus acts as a central integrator for processing and relaying sensory and motor information to and from the cerebral cortex, and the habenula plays pivotal roles in emotive decision making by modulating dopaminergic and serotonergic circuits. These neural compartments are derived from a common developmental progenitor domain, called prosomere 2, in the caudal forebrain. Thalamic and habenular neurons exhibit distinct molecular profile, neurochemical identity, and axonal circuitry. However, the mechanisms of how their progenitors in prosomere 2 give rise to these two populations of neurons and contribute to the forebrain circuitry remains unclear...
February 17, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28198454/preliminary-evidence-for-a-role-of-the-adrenergic-nervous-system-in-generalized-anxiety-disorder
#4
Xiaobin Zhang, Joanna Norton, Isabelle Carrière, Karen Ritchie, Isabelle Chaudieu, Joanne Ryan, Marie-Laure Ancelin
Generalized anxiety disorder (GAD) is a common chronic condition that is understudied compared to other psychiatric disorders. An altered adrenergic function has been reported in GAD, however direct evidence for genetic susceptibility is missing. This study evaluated the associations of gene variants in adrenergic receptors (ADRs) with GAD, with the involvement of stressful events. Data were obtained from 844 French community-dwelling elderly aged 65 or over. Anxiety disorders were assessed using the Mini-International Neuropsychiatry Interview, according to DSM-IV criteria...
February 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28183453/glucose-tolerance-and-free-fatty-acid-metabolism-in-adults-with-variations-in-tcf7l2-rs7903146
#5
Jin Lu, Ron T Varghese, Lianzhen Zhou, Adrian Vella, Michael D Jensen
OBJECTIVE: TCF7L2 variant rs7903146 is associated with increased risk for type 2 diabetes. We investigated the effect of TCF7L2 variant rs7903146 and glucose tolerance on free fatty acid (FFA) metabolism. RESEARCH DESIGN AND METHODS: We recruited 120 individuals, half homozygous for the major CC allele and half homozygous for the minor TT allele at rs7903146; each underwent a 2-h, 75g oral glucose tolerance test (OGTT). Plasma glucose, insulin and free fatty acid concentrations were measured on blood collected before and during the OGTT...
March 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28165569/effect-of-mir-212-targeting-tcf7l2-on-the-proliferation-and-metastasis-of-cervical-cancer
#6
C Zhou, D-M Tan, L Chen, X-Y Xu, C-C Sun, L-J Zong, S Han, Y-Z Zhang
OBJECTIVE: MicroRNAs (miRs) function as either oncogenes or tumor suppressors in the progression of various human cancers, including cervical cancer. This study aimed to explore the role of miR-212 in cervical cancer and the mechanisms underlying this role. PATIENTS AND METHODS: Quantitative real-time polymerase chain reaction (RT-PCR) and Western blot assays were used to determine the expression levels of miR-212 and TCF7L2 in the cervical cancer cells. Cell proliferation invasion was examined using BrdU assays and transwell, respectively...
January 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28143522/aspirin-intervention-for-the-reduction-of-colorectal-cancer-risk-aspired-a-study-protocol-for-a-randomized-controlled-trial
#7
David A Drew, Samantha M Chin, Katherine K Gilpin, Melanie Parziale, Emily Pond, Madeline M Schuck, Kathleen Stewart, Meaghan Flagg, Crystal A Rawlings, Vadim Backman, Peter J Carolan, Daniel C Chung, Francis P Colizzo, Matthew Freedman, Manish Gala, John J Garber, Curtis Huttenhower, Dmitriy Kedrin, Hamed Khalili, Douglas S Kwon, Sanford D Markowitz, Ginger L Milne, Norman S Nishioka, James M Richter, Hemant K Roy, Kyle Staller, Molin Wang, Andrew T Chan
BACKGROUND: Although aspirin is recommended for the prevention of colorectal cancer, the specific individuals for whom the benefits outweigh the risks are not clearly defined. Moreover, the precise mechanisms by which aspirin reduces the risk of cancer are unclear. We recently launched the ASPirin Intervention for the REDuction of colorectal cancer risk (ASPIRED) trial to address these uncertainties. METHODS/DESIGN: ASPIRED is a prospective, double-blind, multidose, placebo-controlled, biomarker clinical trial of aspirin use in individuals previously diagnosed with colorectal adenoma...
February 1, 2017: Trials
https://www.readbyqxmd.com/read/28139539/association-of-type-2-diabetes-mellitus-genes-in-polycystic-ovary-syndrome-aetiology-among-women-from-southern-india
#8
Battini Mohan Reddy, Uma Jyothi Kommoju, Shilpi Dasgupta, Pranavchand Rayabarapu
BACKGROUND & OBJECTIVES: Polycystic ovary syndrome (PCOS) is the most common reproductive endocrine disorder of premenopausal women. Given the phenotypic overlap between PCOS and type 2 diabetes mellitus (T2DM), this study was carried out to investigate whether genes implicated in T2DM were also involved in the susceptibility to PCOS among women from southern India. METHODS: A total of 248 women with PCOS and 210 healthy women as controls were genotyped for a panel of 15 single nucleotide polymorphisms (SNPs) from the nine T2DM genes, such as TCF7L2, IGF2BP2, SLC30A8, HHEX, CDKAL1, CDKN2A, IRS1, CAPN10 and PPARG, on Sequenom MassARRAY platform...
September 2016: Indian Journal of Medical Research
https://www.readbyqxmd.com/read/28133617/molecular-analysis-of-a-genetic-variants-panel-related-to-nutrients-and-metabolism-association-with-susceptibility-to-gestational-diabetes-and-cardiometabolic-risk-in-affected-women
#9
Marica Franzago, Federica Fraticelli, Antonio Nicolucci, Claudio Celentano, Marco Liberati, Liborio Stuppia, Ester Vitacolonna
Gestational diabetes mellitus (GDM) is the most frequent metabolic disorder in pregnancy. Women with a GDM history are at increased risk of developing diabetes and cardiovascular diseases. Studies have demonstrated a significant correlation between several genes involved in the metabolic pathway of insulin and environmental factors. The aim of this study was to investigate the relationship between clinical parameters in GDM and variants in genes involved with nutrients and metabolism. Several variants PPARG2 rs1801282 (C>G); PPARGC1A rs8192678 (C>T); TCF7L2 rs7903146 (C>T); LDLR rs2228671 (C>T); MTHFR rs1801133 (C>T); APOA5 rs662799 (T>C); GCKR rs1260326 (C>T); FTO rs9939609 (T>A); MC4R rs17782313 (T>C) were genotyped in 168 pregnant Caucasian women with or without GDM by High Resolution Melting (HRM) analysis...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/28122918/nuclear-factor-i-c-reciprocally-regulates-adipocyte-and-osteoblast-differentiation-via-control-of-canonical-wnt-signaling
#10
Jie Zhou, Shan Wang, Qi Qi, Xiaoyue Yang, Endong Zhu, Hairui Yuan, Xuemei Li, Ying Liu, Xiaoxia Li, Baoli Wang
Nuclear factor I-C (NFIC) has recently been identified as an important player in osteogenesis and bone homeostasis in vivo However, the molecular mechanisms involved have yet to be defined. In the current study, Nfic expression was altered in primary marrow stromal cells and established progenitor lines after adipogenic and osteogenic treatment. Overexpression of Nfic in stromal cells ST2, mesenchymal cells C3H10T1/2, and primary marrow stromal cells inhibited adipogenic differentiation, whereas it promoted osteogenic differentiation...
January 25, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28117839/the-genetic-overlap-between-mood-disorders-and-cardiometabolic-diseases-a-systematic-review-of-genome-wide-and-candidate-gene-studies
#11
REVIEW
A T Amare, K O Schubert, M Klingler-Hoffmann, S Cohen-Woods, B T Baune
Meta-analyses of genome-wide association studies (meta-GWASs) and candidate gene studies have identified genetic variants associated with cardiovascular diseases, metabolic diseases and mood disorders. Although previous efforts were successful for individual disease conditions (single disease), limited information exists on shared genetic risk between these disorders. This article presents a detailed review and analysis of cardiometabolic diseases risk (CMD-R) genes that are also associated with mood disorders...
January 24, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28117551/identification-of-ferm-domain-containing-protein-5-frmd5-as-a-novel-target-of-%C3%AE-catenin-tcf7l2-complex
#12
Chi Zhu, Kiyoshi Yamaguchi, Tomoyuki Ohsugi, Yumi Terakado, Rei Noguchi, Tsuneo Ikenoue, Yoichi Furukawa
Deregulation of the canonical Wnt signaling pathway plays an important role in human tumorigenesis through the accumulation of β-catenin and subsequent transactivation of TCF7L2. Although some of the consequences associated with the accumulated β-catenin have been clarified, the comprehensive effect of activated β-catenin/TCF7L2 transcriptional complex on tumorigenesis remains to be elucidated. To understand the precise molecular mechanisms underlying colorectal cancer, we searched for genes regulated by the complex in colorectal tumors...
January 24, 2017: Cancer Science
https://www.readbyqxmd.com/read/28102847/curcumin-represses-mouse-3t3-l1-cell-adipogenic-differentiation-via-inhibiting-mir-17-5p-and-stimulating-the-wnt-signalling-pathway-effector-tcf7l2
#13
Lili Tian, Zhuolun Song, Weijuan Shao, William W Du, Lisa R Zhao, Kejing Zeng, Burton B Yang, Tianru Jin
Understanding mechanisms underlying adipogenic differentiation may lead to the discovery of novel therapeutic targets for obesity. Wnt signalling pathway activation leads to repressed adipogenic differentiation while certain microRNAs may regulate pre-adipocyte proliferation and differentiation. We show here that in mouse white adipose tissue, miR-17-5p level is elevated after high fat diet consumption. miR-17-5p upregulates adipogenic differentiation, as its over-expression increased while its inhibition repressed 3T3-L1 differentiation...
January 19, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28101933/associations-of-common-variants-in-the-slc16a11-tcf7l2-and-abca1-genes-with-pediatric-onset-type-2-diabetes-and-related-glycemic-traits-in-families-a-case-control-and-case-parent-trio-study
#14
América L Miranda-Lora, Miguel Cruz, Mario Molina-Díaz, Jorge Gutiérrez, Samuel Flores-Huerta, Miguel Klünder-Klünder
BACKGROUND: There is evidence of associations of single-nucleotide polymorphisms (SNPs) with type 2 diabetes (T2D) and related glycemic traits in adults, but there is a little information about such associations in youths. OBJECTIVE: The aim of this study was to evaluate the associations of SNPs in the TCF7L2, SLC16A11, and ABCA1 genes with T2D and related glycemic traits in Mexican children and adolescents. SUBJECTS: A total of 99 families with children with T2D (n = 327) and 83 families with children without the disease (n = 212)...
January 19, 2017: Pediatric Diabetes
https://www.readbyqxmd.com/read/28072873/association-study-with-77-snps-confirms-the-robust-role-for-the-rs10830963-g-of-mtnr1b-variant-and-identifies-two-novel-associations-in-gestational-diabetes-mellitus-development
#15
Klara Rosta, Zahra Al-Aissa, Orsolya Hadarits, Jürgen Harreiter, Ákos Nádasdi, Fanni Kelemen, Dagmar Bancher-Todesca, Zsolt Komlósi, László Németh, János Rigó, István Sziller, Anikó Somogyi, Alexandra Kautzky-Willer, Gábor Firneisz
CONTEXT: Genetic variation in human maternal DNA contributes to the susceptibility for development of gestational diabetes mellitus (GDM). OBJECTIVE: We assessed 77 maternal single nucleotide gene polymorphisms (SNPs) for associations with GDM or plasma glucose levels at OGTT in pregnancy. METHODS: 960 pregnant women (after dropouts 820: case/control: m99'WHO: 303/517, IADPSG: 287/533) were enrolled in two countries into this case-control study...
2017: PloS One
https://www.readbyqxmd.com/read/28067832/type-2-diabetes-susceptibility-in-the-greek-cypriot-population-replication-of-associations-with-tcf7l2-fto-hhex-slc30a8-and-igf2bp2-polymorphisms
#16
Christina Votsi, Costas Toufexis, Kyriaki Michailidou, Athos Antoniades, Nicos Skordis, Minas Karaolis, Constantinos S Pattichis, Kyproula Christodoulou
Type 2 diabetes (T2D) has been the subject of numerous genetic studies in recent years which revealed associations of the disease with a large number of susceptibility loci. We hereby initiate the evaluation of T2D susceptibility loci in the Greek-Cypriot population by performing a replication case-control study. One thousand and eighteen individuals (528 T2D patients, 490 controls) were genotyped at 21 T2D susceptibility loci, using the allelic discrimination method. Statistically significant associations of T2D with five of the tested single nucleotide polymorphisms (SNPs) (TCF7L2 rs7901695, FTO rs8050136, HHEX rs5015480, SLC30A8 rs13266634 and IGF2BP2 rs4402960) were observed in this study population...
January 6, 2017: Genes
https://www.readbyqxmd.com/read/28060743/2017-update-on-the-relationship-between-diabetes-and-colorectal-cancer-epidemiology-potential-molecular-mechanisms-and-therapeutic-implications
#17
REVIEW
Nieves González, Isabel Prieto, Laura Del Puerto-Nevado, Sergio Portal-Nuñez, Juan Antonio Ardura, Marta Corton, Beatriz Fernández-Fernández, Oscar Aguilera, Carmen Gomez-Guerrero, Sebastián Mas, Juan Antonio Moreno, Marta Ruiz-Ortega, Ana Belen Sanz, Maria Dolores Sanchez-Niño, Federico Rojo, Fernando Vivanco, Pedro Esbrit, Carmen Ayuso, Gloria Alvarez-Llamas, Jesús Egido, Jesús García-Foncillas, Alberto Ortiz, Diabetes Cancer Connect Consortium
Worldwide deaths from diabetes mellitus (DM) and colorectal cancer increased by 90% and 57%, respectively, over the past 20 years. The risk of colorectal cancer was estimated to be 27% higher in patients with type 2 DM than in non-diabetic controls. However, there are potential confounders, information from lower income countries is scarce, across the globe there is no correlation between DM prevalence and colorectal cancer incidence and the association has evolved over time, suggesting the impact of additional environmental factors...
January 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28052964/whole-genome-bisulfite-sequencing-of-human-pancreatic-islets-reveals-novel-differentially-methylated-regions-in-type-2-diabetes-pathogenesis
#18
Petr Volkov, Karl Bacos, Jones K Ofori, Jonathan Lou S Esguerra, Lena Eliasson, Tina Rönn, Charlotte Ling
Current knowledge about the role of epigenetics in type 2 diabetes (T2D) remains limited. Only a few studies have investigated DNA methylation of selected candidate genes or a very small fraction of genomic CpG sites in human pancreatic islets, the tissue of primary pathogenic importance for diabetes. Our aim was to characterize the whole-genome DNA methylation landscape in human pancreatic islets, to identify differentially methylated regions (DMRs) in diabetic islets, and to investigate the function of DMRs in islet biology...
January 4, 2017: Diabetes
https://www.readbyqxmd.com/read/28040731/quantifying-the-extent-to-which-index-event-biases-influence-large-genetic-association-studies
#19
Hanieh Yaghootkar, Michael P Bancks, Sam E Jones, Aaron McDaid, Robin Beaumont, Louise Donnelly, Andrew R Wood, Archie Campbell, Jessica Tyrrell, Lynne J Hocking, Marcus A Tuke, Katherine S Ruth, Ewan R Pearson, Anna Murray, Rachel M Freathy, Patricia B Munroe, Caroline Hayward, Colin Palmer, Michael N Weedon, James S Pankow, Timothy M Frayling, Zoltán Kutalik
As genetic association studies increase in size to 100,000s of individuals, subtle biases may influence conclusions. One possible bias is "index event bias" (IEB) that appears due to the stratification by, or enrichment for, disease status when testing associations between genetic variants and a disease-associated trait. We aimed to test the extent to which IEB influences some known trait associations in a range of study designs and provide a statistical framework for assessing future associations. Analysing data from 113,203 non-diabetic UK Biobank participants, we observed three (near TCF7L2, CDKN2AB and CDKAL1) overestimated (BMI-decreasing) and one (near MTNR1B) underestimated (BMI-increasing) associations among 11 type 2 diabetes risk alleles (at P < 0...
December 30, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/28002797/targeted-exome-sequencing-reveals-distinct-pathogenic-variants-in-iranians-with-colorectal-cancer
#20
Hassan Ashktorab, Pooneh Mokarram, Hamed Azimi, Hasti Olumi, Sudhir Varma, Michael L Nickerson, Hassan Brim
PURPOSE: Next Generation Sequencing (NGS) is currently used to establish mutational profiles in many multigene diseases such as colorectal cancer (CRC), which is on the rise in many parts of the developing World including, Iran. Little is known about its genetic hallmarks in these populations. AIM: To identify variants in 15 CRC-associated genes in patients of Iranian descent. RESULTS: There were 51 validated variants distributed on 12 genes: 22% MSH3 (n = 11/51), 10% MSH6 (n = 5/51), 8% AMER1 (n = 4/51), 20% APC (n = 10/51), 2% BRAF (n = 1/51), 2% KRAS (n = 1/51), 12% PIK3CA (n = 6/51), 8% TGFβR2A (n = 4/51), 2% SMAD4 (n = 1/51), 4% SOX9 (n = 2/51), 6% TCF7L2 (n = 3/51), and 6% TP53 (n = 3/51)...
January 31, 2017: Oncotarget
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