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https://www.readbyqxmd.com/read/28438156/relative-contribution-of-type-1-and-type-2-diabetes-loci-to-the-genetic-etiology-of-adult-onset-non-insulin-requiring-autoimmune-diabetes
#1
Rajashree Mishra, Alessandra Chesi, Diana L Cousminer, Mohammad I Hawa, Jonathan P Bradfield, Kenyaita M Hodge, Vanessa C Guy, Hakon Hakonarson, Didac Mauricio, Nanette C Schloot, Knud B Yderstræde, Benjamin F Voight, Stanley Schwartz, Bernhard O Boehm, Richard David Leslie, Struan F A Grant
BACKGROUND: In adulthood, autoimmune diabetes can present as non-insulin-requiring diabetes, termed as 'latent autoimmune diabetes in adults' (LADA). In this study, we investigated established type 1 diabetes (T1D) and type 2 diabetes (T2D) genetic loci in a large cohort of LADA cases to assess where LADA is situated relative to these two well-characterized, classic forms of diabetes. METHODS: We tested the association of T1D and T2D GWAS-implicated loci in 978 LADA cases and 1057 non-diabetic controls of European ancestry using a linear mixed model...
April 25, 2017: BMC Medicine
https://www.readbyqxmd.com/read/28430825/discovery-and-fine-mapping-of-adiposity-loci-using-high-density-imputation-of-genome-wide-association-studies-in-individuals-of-african-ancestry-african-ancestry-anthropometry-genetics-consortium
#2
Maggie C Y Ng, Mariaelisa Graff, Yingchang Lu, Anne E Justice, Poorva Mudgal, Ching-Ti Liu, Kristin Young, Lisa R Yanek, Mary F Feitosa, Mary K Wojczynski, Kristin Rand, Jennifer A Brody, Brian E Cade, Latchezar Dimitrov, Qing Duan, Xiuqing Guo, Leslie A Lange, Michael A Nalls, Hayrettin Okut, Salman M Tajuddin, Bamidele O Tayo, Sailaja Vedantam, Jonathan P Bradfield, Guanjie Chen, Wei-Min Chen, Alessandra Chesi, Marguerite R Irvin, Badri Padhukasahasram, Jennifer A Smith, Wei Zheng, Matthew A Allison, Christine B Ambrosone, Elisa V Bandera, Traci M Bartz, Sonja I Berndt, Leslie Bernstein, William J Blot, Erwin P Bottinger, John Carpten, Stephen J Chanock, Yii-Der Ida Chen, David V Conti, Richard S Cooper, Myriam Fornage, Barry I Freedman, Melissa Garcia, Phyllis J Goodman, Yu-Han H Hsu, Jennifer Hu, Chad D Huff, Sue A Ingles, Esther M John, Rick Kittles, Eric Klein, Jin Li, Barbara McKnight, Uma Nayak, Barbara Nemesure, Adesola Ogunniyi, Andrew Olshan, Michael F Press, Rebecca Rohde, Benjamin A Rybicki, Babatunde Salako, Maureen Sanderson, Yaming Shao, David S Siscovick, Janet L Stanford, Victoria L Stevens, Alex Stram, Sara S Strom, Dhananjay Vaidya, John S Witte, Jie Yao, Xiaofeng Zhu, Regina G Ziegler, Alan B Zonderman, Adebowale Adeyemo, Stefan Ambs, Mary Cushman, Jessica D Faul, Hakon Hakonarson, Albert M Levin, Katherine L Nathanson, Erin B Ware, David R Weir, Wei Zhao, Degui Zhi, Donna K Arnett, Struan F A Grant, Sharon L R Kardia, Olufunmilayo I Oloapde, D C Rao, Charles N Rotimi, Michele M Sale, L Keoki Williams, Babette S Zemel, Diane M Becker, Ingrid B Borecki, Michele K Evans, Tamara B Harris, Joel N Hirschhorn, Yun Li, Sanjay R Patel, Bruce M Psaty, Jerome I Rotter, James G Wilson, Donald W Bowden, L Adrienne Cupples, Christopher A Haiman, Ruth J F Loos, Kari E North
Genome-wide association studies (GWAS) have identified >300 loci associated with measures of adiposity including body mass index (BMI) and waist-to-hip ratio (adjusted for BMI, WHRadjBMI), but few have been identified through screening of the African ancestry genomes. We performed large scale meta-analyses and replications in up to 52,895 individuals for BMI and up to 23,095 individuals for WHRadjBMI from the African Ancestry Anthropometry Genetics Consortium (AAAGC) using 1000 Genomes phase 1 imputed GWAS to improve coverage of both common and low frequency variants in the low linkage disequilibrium African ancestry genomes...
April 21, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28420445/investigation-of-the-association-between-the-tcf7l2-rs7903146-c-t-gene-polymorphism-and-obesity-in-a-cameroonian-population-a-pilot-study
#3
Aurelie Nguimmo-Metsadjio, Barbara Atogho-Tiedeu, Jean Jacques N Noubiap, Marie-Solange Evehe, Rosine Djokam-Dadjeu, Olivier Sontsa Donfack, Dieudonne Nanfa, Edith Pascale M Mato, Elvis Ndonwi Ngwa, Magellan Guewo-Fokeng, Priscille Pokam-Fosso, Wilfred F Mbacham, Jean Claude Mbanya, Eugene Sobngwi
OBJECTIVE: This study aimed at investigating the association between the rs7903146 (C/T) polymorphism of the TCF7L2 gene with obesity in a Cameroonian population. METHOD: This was a case-control pilot study including 61 obese and 61 non-obese Cameroonian adults. Anthropometric indices of obesity, blood pressure, fasting blood glucose, and blood lipids were measured. The rs7903146 (C/T) polymorphism of the TCF7L2 gene was genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and genotypes were correlated with clinical and biological parameters...
April 18, 2017: Journal of Health, Population, and Nutrition
https://www.readbyqxmd.com/read/28404897/tcf7l2-polymorphisms-and-the-risk-of-schizophrenia-in-the-chinese-han-population
#4
Lijun Liu, Jingjie Li, Mengdan Yan, Jing Li, Junyu Chen, Yi Zhang, Xikai Zhu, Li Wang, Longli Kang, Dongya Yuan, Tianbo Jin
Single nucleotide polymorphisms (SNPs) in TCF7L2 (Transcription Factor 7-Like 2) reportedly affect susceptibility to schizophrenia (SCZ). We examined the association between TCF7L2 polymorphisms and SCZ susceptibility in a Chinese Han population. Six SNPs were genotyped in 499 SCZ patients and 500 healthy individuals, after which their associations with SCZ were evaluated using the Chi-squared test and genetic model analyses. We observed that the allele A of rs12573128 is associated with an increased SCZ risk (odds ratio [OR] = 1...
February 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28369879/human-skeletal-muscle-fibroblasts-stimulate-in-vitro-myogenesis-and-in-vivo-muscle-regeneration
#5
Abigail L Mackey, Mélanie Magnan, Bénédicte Chazaud, Michael Kjaer
Accumulation of skeletal muscle extracellular matrix is an unfavourable characteristic of many muscle diseases, muscle injury and sarcopenia. In addition to the indispensable role satellite cells play in muscle regeneration, there is emerging evidence in rodents for a regulatory influence on fibroblast activity. However the influence of fibroblasts on satellite cells and muscle regeneration in humans is unknown. The purpose of this study was to investigate this in vitro and during in vivo regeneration in humans...
March 30, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28362475/the-genetic-basis-of-obesity-complications
#6
Katarzyna Skrypnik, Joanna Suliburska, Damian Skrypnik, Łukasz Pilarski, Julita Reguła, Paweł Bogdański
Intensive research is currently being performed into the genetic background of excess body mass compli- cations such as diabetes, cardiovascular disorders, especially atherosclerosis and coronary heart disease. Chronic inflammation is an important process in the pathogenesis of obesity, wherein there is an aberrant ex- pression of genes encoding adipokines. Visceral tissue is characterized by a higher expression and secretion of interleukin-8, interleukin-1ß and plasminogen activator inhibitor 1 in the subcutaneous tissue secretion of leptin prevails...
January 2017: Acta Scientiarum Polonorum. Technologia Alimentaria
https://www.readbyqxmd.com/read/28352326/genetic-variants-in-kcnj11-tcf7l2-and-hnf4a-are-associated-with-type-2-diabetes-bmi-and-dyslipidemia-in-families-of-northeastern-mexico-a-pilot-study
#7
Hugo Leonid Gallardo-Blanco, Jesus Zacarías Villarreal-Perez, Ricardo Martin Cerda-Flores, Andres Figueroa, Celia Nohemi Sanchez-Dominguez, Juana Mercedes Gutierrez-Valverde, Iris Carmen Torres-Muñoz, Fernando Javier Lavalle-Gonzalez, Esther Carlota Gallegos-Cabriales, Laura Elia Martinez-Garza
The aim of the present study was to investigate whether genetic markers considered risk factors for metabolic syndromes, including dyslipidemia, obesity and type 2 diabetes mellitus (T2DM), can be applied to a Northeastern Mexican population. A total of 37 families were analyzed for 63 single nucleotide polymorphisms (SNPs), and the age, body mass index (BMI), glucose tolerance values and blood lipid levels, including those of cholesterol, low-density lipoprotein (LDL), very LDL (VLDL), high-density lipoprotein (HDL) and triglycerides were evaluated...
February 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28351929/genetic-heterogeneity-in-therapy-na%C3%A3-ve-synchronous-primary-breast-cancers-and-their-metastases
#8
François-Clément Bidard, Charlotte K Y Ng, Salvatore Piscuoglio, Felipe C Geyer, Reymond Lim, Ino De Bruijn, Ronglai Shen, Fresia Pareja, Samuel Berman, Lu Wang, Jean-Yves Pierga, Anne Vincent-Salomon, Agnes Viale, Larry Norton, Brigitte Sigal, Britta Weigelt, Paul Cotu, Jorge S Reis-Filho
PURPOSE: Paired primary breast cancers and metachronous metastases after adjuvant treatment differed in their clonal composition and genetic alterations, but it is unclear whether the differences stem from the selective pressures of the metastatic process, the systemic therapies or both. We sought to define the repertoire of genetic alterations in breast cancer patients with de novo metastatic disease who had not received local or systemic therapy. EXPERIMENTAL DESIGN: Up to two anatomically distinct core biopsies of primary breast cancers and synchronous distant metastases from nine patients who presented with metastatic disease were subjected to high-depth whole-exome sequencing...
March 28, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28343277/pancreatic-alpha-cell-selective-deletion-of-tcf7l2-impairs-glucagon-secretion-and-counter-regulatory-responses-to-hypoglycaemia-in-mice
#9
Gabriela da Silva Xavier, Angeles Mondragon, Vishnou Mourougavelou, Céline Cruciani-Guglielmacci, Jessica Denom, Pedro Luis Herrera, Christophe Magnan, Guy A Rutter
AIMS/HYPOTHESIS: Transcription factor 7-like 2 (TCF7L2) is a high mobility group (HMG) box-containing transcription factor and downstream effector of the Wnt signalling pathway. SNPs in the TCF7L2 gene have previously been associated with an increased risk of type 2 diabetes in genome-wide association studies. In animal studies, loss of Tcf7l2 function is associated with defective islet beta cell function and survival. Here, we explore the role of TCF7L2 in the control of the counter-regulatory response to hypoglycaemia by generating mice with selective deletion of the Tcf7l2 gene in pancreatic alpha cells...
March 25, 2017: Diabetologia
https://www.readbyqxmd.com/read/28343235/transcription-dependent-radial-distribution-of-tcf7l2-regulated-genes-in-chromosome-territories
#10
Keyvan Torabi, Darawalee Wangsa, Immaculada Ponsa, Markus Brown, Anna Bosch, Maria Vila-Casadesús, Tatiana S Karpova, Maria Calvo, Antoni Castells, Rosa Miró, Thomas Ried, Jordi Camps
Human chromosomes occupy distinct territories in the interphase nucleus. Such chromosome territories (CTs) are positioned according to gene density. Gene-rich CTs are generally located in the center of the nucleus, while gene-poor CTs are positioned more towards the nuclear periphery. However, the association between gene expression levels and the radial positioning of genes within the CT is still under debate. In the present study, we performed three-dimensional fluorescence in situ hybridization experiments in the colorectal cancer cell lines DLD-1 and LoVo using whole chromosome painting probes for chromosomes 8 and 11 and BAC clones targeting four genes with different expression levels assessed by gene expression arrays and RT-PCR...
March 25, 2017: Chromosoma
https://www.readbyqxmd.com/read/28330327/role-of-gnb3-net-kcnj11-tcf7l2-and-grl-genes-single-nucleotide-polymorphism-in-the-risk-prediction-of-type-2-diabetes-mellitus
#11
REVIEW
Saliha Rizvi, Syed Tasleem Raza, Qamar Rahman, Farzana Mahdi
Type 2 diabetes (T2DM) is a polygenic metabolic disorder characterized by hyperglycemia occurring as a result of impaired insulin secretion or insulin resistance. Various environmental and genetic factors interact and increase the risk of T2DM and its complications. Among the various genetic factors associated with T2DM, single nucleotide polymorphism in different candidate genes have been studied intensively and the resulting genetic variants have been found to have either positive or negative association with T2DM thereby increasing or decreasing the risk of T2DM, respectively...
December 2016: 3 Biotech
https://www.readbyqxmd.com/read/28303247/effect-of-wnt-signaling-on-the-differentiation-of-islet-%C3%AE-cells-from-adipose-derived-stem-cells
#12
Hefei Wang, Yu Ren, Xiao Hu, Min Ma, Xiao Wang, Hao Liang, Dongjun Liu
The Wnt signaling is critical for pancreatic development and islet function; however, its precise effects on the development and function of the β-cells remain controversial. Here we examined mRNA and protein expression of components of the Wnt signaling throughout the differentiation of islet β-cells from adipose-derived stem cells (ADSCs). After induction, ADSCs expressed markers of β-cells, including the insulin, PDX1, and glucagon genes, and the PDX1, CK19, nestin, insulin, and C-peptide proteins, indicating their successful differentiation...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28299838/pilot-cohort-study-on-the-potential-role-of-tcf7l2-rs7903146-on-ischemic-heart-disease-among-non-diabetic-kidney-transplant-recipients
#13
Marco Quaglia, Claudio Musetti, Guido Merlotti, Armando A Genazzani, Sarah Cargnin, Tiziana Cena, Vincenzo Cantaluppi, Salvatore Terrazzino
BACKGROUND: TCF7L2 rs7903146 C>T polymorphism is associated with diabetes in the general population but its independent impact on cardiovascular disease is debated. On this basis, we investigated its association with major adverse cardiac events (MACE) in a single-center cohort of non-diabetic kidney transplant recipients (KTRs). METHODS: Patients with pretransplant diabetes were excluded and patients who developed post-transplant diabetes were censored at time of diagnosis...
March 16, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/28277135/tcf7l2-capn10-polymorphisms-are-associated-with-gestational-diabetes-mellitus-gdm-risks-a-meta-analysis
#14
Zhi Hou, Ming Li, Yanmin Cao
Several polymorphisms have been identified in transcription factor 7-like 2 (TCF7L2), and calpain-10 (CAPN10) genes. Controversial conclusions for the genetic relationship between these polymorphisms and gestational diabetes mellitus (GDM) risks were obtained. Our study aims at assessing whether these polymorphisms are associated with GDM susceptibility via a meta-analysis. A total of 19 eligible case-control articles were obtained after databases searching. A significantly increased GDM risk was observed for TCF7L2 rs7903146 (all OR > 1, p < 0...
February 21, 2017: Gynecological Endocrinology
https://www.readbyqxmd.com/read/28254843/genetics-of-type-2-diabetes-in-u-s-hispanic-latino-individuals-results-from-the-hispanic-community-health-study-study-of-latinos-hchs-sol
#15
Qibin Qi, Adrienne M Stilp, Tamar Sofer, Jee-Young Moon, Bertha Hidalgo, Adam A Szpiro, Tao Wang, Maggie C Y Ng, Xiuqing Guo, Yii-Der Ida Chen, Kent D Taylor, M Larissa Aviles-Santa, George Papanicolaou, James S Pankow, Neil Schneiderman, Cathy C Laurie, Jerome I Rotter, Robert C Kaplan
Few genome-wide association studies (GWAS) of type 2 diabetes (T2D) have been conducted in US Hispanics/Latinos of diverse backgrounds who are disproportionately affected by diabetes. We conducted a GWAS in 2499 T2D cases and 5247 controls from 6 Hispanic/Latino background groups in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Our GWAS identified two known loci (TCF7L2 and KCNQ1) reaching genome-wide significance level. Conditional analysis on known index SNPs indicated an additional independent signal at KCNQ1, represented by an African ancestry-specific variant, rs1049549 (OR=1...
March 2, 2017: Diabetes
https://www.readbyqxmd.com/read/28253288/a-novel-tcf7l2-type-2-diabetes-snp-identified-from-fine-mapping-in-african-american-women
#16
Stephen A Haddad, Julie R Palmer, Kathryn L Lunetta, Maggie C Y Ng, Edward A Ruiz-Narváez
SNP rs7903146 in the Wnt pathway's TCF7L2 gene is the variant most significantly associated with type 2 diabetes to date, with associations observed across diverse populations. We sought to determine whether variants in other Wnt pathway genes are also associated with this disease. We evaluated 69 genes involved in the Wnt pathway, including TCF7L2, for associations with type 2 diabetes in 2632 African American cases and 2596 controls from the Black Women's Health Study. Tag SNPs for each gene region were genotyped on a custom Affymetrix Axiom Array, and imputation was performed to 1000 Genomes Phase 3 data...
2017: PloS One
https://www.readbyqxmd.com/read/28220878/homozygous-carriers-of-the-tcf7l2-rs7903146-t-allele-show-altered-postprandial-response-in-triglycerides-and-triglyceride-rich-lipoproteins
#17
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
#18
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
#19
Myungsin Lee, Jiyeon Yoon, Hobeom Song, Bumwhee Lee, Duc Tri Lam, 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...
April 1, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28198454/preliminary-evidence-for-a-role-of-the-adrenergic-nervous-system-in-generalized-anxiety-disorder
#20
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
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