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https://www.readbyqxmd.com/read/29326107/tcf7l2-genetic-variation-augments-incretin-resistance-and-influences-response-to-a-sulfonylurea-and-metformin-the-study-to-understand-the-genetics-of-the-acute-response-to-metformin-and-glipizide-in-humans-sugar-mgh
#1
Shylaja Srinivasan, Varinderpal Kaur, Bindu Chamarthi, Katherine R Littleton, Ling Chen, Alisa K Manning, Jordi Merino, Melissa K Thomas, Margo Hudson, Allison Goldfine, Jose C Florez
OBJECTIVE: The rs7903146 T allele in transcription-factor-7-like-2 (TCF7L2) is strongly associated with type 2 diabetes (T2D), but the mechanisms for increased risk remain unclear. We evaluated the physiologic and hormonal effects of TCF7L2 genotype before and after interventions that influence glucose physiology. RESEARCH DESIGN AND METHODS: We genotyped rs7903146 in 608 individuals without diabetes and recorded biochemical data before and after one dose of glipizide (5 mg) on visit 1, and a 75-g oral glucose tolerance test (OGTT) performed after administration of metformin 500 mg twice daily over 2 days...
January 11, 2018: Diabetes Care
https://www.readbyqxmd.com/read/29325775/nutrigenetic-variants-and-cardio-metabolic-risk-in-women-with-or-without-gestational-diabetes
#2
Marica Franzago, Federica Fraticelli, Daniela Marchetti, Claudio Celentano, Marco Liberati, Liborio Stuppia, Ester Vitacolonna
AIM: Gestational diabetes mellitus (GDM) is the most frequent metabolic disorder in pregnancy and it can be considered a silent risk associated to T2DM and CVD later in life. The aim of this study was to investigate the association of clinical parameters with nine single nucleotide polymorphisms (SNPs) involved with nutrients and metabolism in women with or without GDM in order to identify potential routine clinical markers for early prevention. METHODS: Nine gene variants associated with nutrients and metabolism, namely 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 104 GDM cases and 124 controls using High Resolution Melting (HRM) analysis...
January 8, 2018: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/29317436/the-diabetes-gene-and-wnt-pathway-effector-tcf7l2-regulates-adipocyte-development-and-function
#3
Xi Chen, Ayala Iriscilla, Chris Shannon, Marcel Fourcaudot, Nikhil K Acharya, Christopher P Jenkinson, Sami Heikkinen, Luke Norton
The gene encoding for transcription factor 7-like 2 (TCF7L2) is the strongest type 2 diabetes (T2DM) candidate gene discovered to date. The TCF7L2 protein is a key transcriptional effector of the Wnt/β-catenin signaling pathway, which is an important developmental pathway that negatively regulates adipogenesis. However, the precise role that TCF7L2 plays in the development and function of adipocytes remains largely unknown. Using a combination of in vitro approaches, we first show that TCF7L2 protein is increased during adipogenesis in 3T3-L1 cells and primary adipocyte stem cells (ASC), and that TCF7L2 expression is required for the regulation of Wnt signaling during adipogenesis...
January 9, 2018: Diabetes
https://www.readbyqxmd.com/read/29314572/high-fat-diet-induced-tcf7l2-promoter-methylation-impairs-%C3%AE-cell-function-in-mouse-pancreatic-islets
#4
Yun Hu, Ping Shi, Ke He, Yun-Qing Zhu, Fan Yang, Min Yang, Bang-Shun He, Xiao-Ming Mao
BACKGROUND: The TCF7L2 (transcription factor 7 like 2) gene is strongly associated with type 2 diabetes (T2D) risk. However, many people without the TCF7L2 at-risk allele develop T2D. The aim of this study was to investigate altered Tcf7l2 DNA methylation and gene expression caused by high-fat diets (HFDs). METHODS: C57BL/6 mice were fed either a HFD or normal diet for 8 weeks and intraperitoneal glucose tolerance tests were performed. Pancreatic islets were sorted for bisulfite sequencing PCR to determine DNA methylation status...
January 4, 2018: Diabetes/metabolism Research and Reviews
https://www.readbyqxmd.com/read/29312594/investigation-of-tcf7l2-lep-and-lepr-polymorphisms-with-esophageal-squamous-cell-carcinomas
#5
Hao Qiu, Xunting Lin, Weifeng Tang, Chao Liu, Yu Chen, Hao Ding, Mingqiang Kang, Shuchen Chen
Single nucleotide polymorphisms (SNPs) in energy metabolism related gene may be key agents in the development of human malignancies. In this study, we aimed to examine the association of transcription factor 7-like 2, Leptin (LEP) and LEP receptor (LEPR) polymorphisms with esophageal squamous cell carcinoma (ESCC). A total of 507 ESCC cases and 1,496 controls were enrolled. We found that LEPR rs6588147 AA genotype was associated with ESCC risk (AA vs. GG/GA: adjusted OR=1.90, 95%CI=1.00-3.61, P=0.049). In the stratified analyses, LEPR rs6588147 G>A polymorphism increased the risk of ESCC (<63 years subgroup: AA vs...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29310734/differential-methylation-of-insulin-like-growth-factor-2-in-offspring-of-physically-active-pregnant-women
#6
M R Marshall, N Paneth, J A Gerlach, L M Mudd, L Biery, D P Ferguson, J M Pivarnik
Several studies have suggested that maternal lifestyle during pregnancy may influence long-term health of offspring by altering the offspring epigenome. Whether maternal leisure-time physical activity (LTPA) during pregnancy might have this effect is unknown. The purpose of this study was to determine the relationship between maternal LTPA during pregnancy and offspring DNA methylation. Participants were recruited from the Archive for Research on Child Health study. At enrollment, participants' demographic information and self-reported LTPA during pregnancy were determined...
January 9, 2018: Journal of Developmental Origins of Health and Disease
https://www.readbyqxmd.com/read/29301589/linking-foxo3-ncoa3-and-tcf7l2-to-ras-pathway-phenotypes-through-a-genome-wide-forward-genetic-screen-in-human-colorectal-cancer-cells
#7
Snehangshu Kundu, Muhammad Akhtar Ali, Niklas Handin, Narendra Padhan, Jimmy Larsson, Maria Karoutsou, Kenneth Ban, Jacek R Wiśniewski, Per Artursson, Liqun He, Mats Hellström, Tobias Sjöblom
BACKGROUND: The Ras pathway genes KRAS, BRAF, or ERBBs have somatic mutations in ~ 60% of human colorectal carcinomas. At present, it is unknown whether the remaining cases lack mutations activating the Ras pathway or whether they have acquired mutations in genes hitherto unknown to belong to the pathway. METHODS: To address the second possibility and extend the compendium of Ras pathway genes, we used genome-wide transposon mutagenesis of two human colorectal cancer cell systems deprived of their activating KRAS or BRAF allele to identify genes enabling growth in low glucose, a Ras pathway phenotype, when targeted...
January 4, 2018: Genome Medicine
https://www.readbyqxmd.com/read/29246974/pancreatic-pericytes-support-beta-cell-function-in-a-tcf7l2-dependent-manner
#8
Lina Sakhneny, Eleonor Rachi, Alona Epshtein, Helen C Guez, Shane Wald-Altman, Michal Lisnyansky, Laura Khalifa-Malka, Adina Hazan, Daria Baer, Avi Priel, Miguel Weil, Limor Landsman
Polymorphism in TCF7L2, a component of the canonical Wnt signaling pathway, has a strong association with β-cell dysfunction and type 2 diabetes through a yet to be defined mechanism. β-Cells rely on cells in their microenvironment, including pericytes, for their proper function. Here, we show that Tcf7l2 activity in pancreatic pericytes is required for β-cell function. Transgenic mice in which Tcf7l2 was selectively inactivated in their pancreatic pericytes exhibited impaired glucose tolerance due to compromised β-cell function and glucose-stimulated insulin secretion...
December 15, 2017: Diabetes
https://www.readbyqxmd.com/read/29245969/decreased-expression-of-interferon-induced-protein-2-ifit2-by-wnt-%C3%AE-catenin-signaling-confers-anti-apoptotic-properties-to-colorectal-cancer-cells
#9
Tomoyuki Ohsugi, Kiyoshi Yamaguchi, Chi Zhu, Tsuneo Ikenoue, Yoichi Furukawa
Impaired Wnt signaling pathway plays a crucial role in the development of colorectal cancer through activation of the β-catenin/TCF7L2 complex. Although genes up-regulated by Wnt/β-catenin signaling have been intensively studied, the roles of down-regulated genes are poorly understood. In this study, we explored a global gene expression of colorectal cancer cells transfected with β-catenin siRNAs or a dominant negative form of TCF7L2 (dnTCF7L2), and identified a set of genes down-regulated by Wnt/β-catenin signaling...
November 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/29220676/penetrance-of-polygenic-obesity-susceptibility-loci-across-the-body-mass-index-distribution
#10
Arkan Abadi, Akram Alyass, Sebastien Robiou du Pont, Ben Bolker, Pardeep Singh, Viswanathan Mohan, Rafael Diaz, James C Engert, Salim Yusuf, Hertzel C Gerstein, Sonia S Anand, David Meyre
A growing number of single-nucleotide polymorphisms (SNPs) have been associated with body mass index (BMI) and obesity, but whether the effects of these obesity-susceptibility loci are uniform across the BMI distribution remains unclear. We studied the effects of 37 BMI-associated SNPs in 75,230 adults of European ancestry across BMI percentiles by using conditional quantile regression (CQR) and meta-regression (MR) models. The effects of nine SNPs (24%)-rs1421085 (FTO; p = 8.69 × 10-15), rs6235 (PCSK1; p = 7...
December 7, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/29193419/effects-of-artichoke-leaf-extract-supplementation-on-metabolic-parameters-in-women-with-metabolic-syndrome-influence-of-tcf7l2-rs7903146-and-fto-rs9939609-polymorphisms
#11
Khatereh Rezazadeh, Mohammad Rahmati-Yamchi, Leila Mohammadnejad, Mehrangiz Ebrahimi-Mameghani, Abbas Delazar
The metabolic syndrome (MetS) is a multicomponent condition with a complex etiology involving genetic and environmental factors. Artichoke leaf extract (ALE) has shown favorable effects on lipid and glucose metabolism. The present study aimed to investigate the effects of ALE supplementation on metabolic parameters in women with MetS, using a nutrigenetics approach. In this double-blind randomized clinical trial, 50 women (aged 20-50 years) with MetS were randomly allocated into the two groups: "ALE group" (received 1,800 mg hydroalcoholic extract of artichoke as four tablets per day) and "placebo group" (received placebo consisted of corn starch, lactose, and avicel as four tablets per day) for 12 weeks...
November 29, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/29190896/cofilin-1-promotes-bladder-cancer-and-is-regulated-by-tcf7l2
#12
Fei Wang, Dinglan Wu, Housheng Fu, Fengrong He, Congjie Xu, Jiaquan Zhou, Daoyuan Li, Guoping Li, Jianbing Xu, Qinghui Wu, Jianxiang Chen, Liangju Su, Weifu Wang, Shufang Zhang
Earlier reports demonstrated that Cofilin expression is increased in bladder cancer samples, though its function remains unknown. Here, we found that Cofilin 1 expression was higher in bladder cancer tissues than in paracancerous tissues. Overexpression of Cofilin 1 promoted, while Cofilin 1 knockdown inhibited, proliferation, migration, and invasion in the T24 and RT4 bladder cancer cell lines. In addition, Cofilin 1 overexpression increased, while Cofilin 1 knockdown decreased, bladder tumor volumes in mouse xenograft experiments...
November 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29182660/interaction-between-tcf7l2-polymorphism-and-dietary-fat-intake-on-high-density-lipoprotein-cholesterol
#13
Dhanasekaran Bodhini, Szilvia Gaal, Israa Shatwan, Kandaswamy Ramya, Basma Ellahi, Shelini Surendran, Vasudevan Sudha, Mohan R Anjana, Viswanathan Mohan, Julie A Lovegrove, Venkatesan Radha, Karani Santhanakrishnan Vimaleswaran
Recent evidence suggests that lifestyle factors influence the association between the Melanocortin 4 receptor (MC4R) and Transcription Factor 7-Like 2 (TCF7L2) gene variants and cardio-metabolic traits in several populations; however, the available research is limited among the Asian Indian population. Hence, the present study examined whether the association between the MC4R single nucleotide polymorphism (SNP) (rs17782313) and two SNPs of the TCF7L2 gene (rs12255372 and rs7903146) and cardio-metabolic traits is modified by dietary factors and physical activity...
2017: PloS One
https://www.readbyqxmd.com/read/29174029/interrelationship-of-the-rs7903146-tcf7l2-gene-variant-with-measures-of-glucose-metabolism-and-adiposity-the-neo-study
#14
R Noordam, C P A Zwetsloot, R de Mutsert, D O Mook-Kanamori, H J Lamb, A de Roos, E J P de Koning, F R Rosendaal, K Willems van Dijk, D van Heemst
BACKGROUND AND AIMS: We investigated the interrelationship of rs7903146-T in TCF7L2 with measures of glucose metabolism and measures of adiposity. METHODS AND RESULTS: This cross-sectional analysis was conducted in 5744 middle-aged participants (mean (standard deviation [SD]) age is 55.9 (6.0) years) from the Netherlands Epidemiology of Obesity (NEO) Study. Associations between rs7903146-T and Type 2 diabetes mellitus (T2D) were assessed with logistic regression...
October 18, 2017: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
https://www.readbyqxmd.com/read/29171469/-risk-of-type-2-diabetes-mellitus-in-the-kyrgyz-population-in-the-presence-of-adipoq-g276t-kcnj11-glu23lys-tcf7l2-ivs3c-t-gene-polymorphisms
#15
Zh T Isakova, E T Talaibekova, D A Asambaeva, A S Kerimkulova, O S Lunegova, N M Aldasheva, A A Aldashev
AIM: To analyze the association of genotype combinations of the polymorphic markers G276T in the ADIPOQ gene, Glu23Lys in the KCNJ11 gene, and IVS3C>T in the TCF7L2 gene with the development of type 2 diabetes mellitus (T2DM) in the Kyrgyz population. SUBJECTS AND METHODS: The investigation enrolled 23 Kyrgyz people, of whom there were 114 patients with T2DM and 109 without T2DM (a control group). T2DM was diagnosed in accordance with the WHO criteria (1999)...
2017: Terapevticheskiĭ Arkhiv
https://www.readbyqxmd.com/read/29135286/vitamin-b12-supplementation-influences-methylation-of-genes-associated-with-type-2-diabetes-and-its-intermediate-traits
#16
Dilip K Yadav, Smeeta Shrestha, Karen A Lillycrop, Charu V Joglekar, Hong Pan, Joanna D Holbrook, Caroline Hd Fall, Chittaranjan S Yajnik, Giriraj R Chandak
AIM: To investigate the effect of B12 and/or folic acid supplementation on genome-wide DNA methylation. METHODS: We performed Infinium HumanMethylation450 BeadChip (Zymo Research, CA, USA) assay in children supplemented with B12 and/or folic acid (n = 12 in each group) and investigated the functional mechanism of selected differentially methylated loci. RESULTS: We noted significant methylation changes postsupplementation in B12 (589 differentially methylated CpGs and 2892 regions) and B12 + folic acid (169 differentially methylated CpGs and 3241 regions) groups...
November 14, 2017: Epigenomics
https://www.readbyqxmd.com/read/29135090/gene-expression-profiling-demonstrates-wnt-%C3%AE-catenin-pathway-genes-alteration-in-mexican-patients-with-colorectal-cancer-and-diabetes-mellitus
#17
Laura Ivonne Wence-Chavez, Ulises Palomares-Chacon, Juan Pablo Flores-Gutierrez, Luis Felipe Jave-Suarez, Adriana Del Carmen Aguilar-Lemarroy, Patricio Barros-Nunez, Silvia Esperanza Flores-Martinez, Jose Sanchez-Corona, Monica Alejandra Rosales-Reynoso
PURPOSE: Several studies have shown a strong association between diabetes mellitus (DM) and increased risk of colorectal cancer (CRC). The fundamental mechanisms that support this association are not entirely understood; however, it is believed that hyperinsulinemia and hyperglycemia may be involved. Some proposed mechanisms include upregulation of mitogenic signaling pathways like MAPK, PI3K, mTOR, and WNT, which are involved in cell proliferation, growth, and cancer cell survival. The purpose of this study was to evaluate the gene expression profile and identify differently expressed genes involved in mitogenic pathways in CRC patients with and without DM...
September 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29131639/proteomic-characterization-of-transcription-and-splicing-factors-associated-with-a-metastatic-phenotype-in-colorectal-cancer
#18
Sofía Torres, Irene García-Palmero, Consuelo Marín-Vicente, Rubén A Bartolomé, Eva Calviño, María Jesús Fernández-Aceñero, J Ignacio Casal
We investigated new transcription and splicing factors associated with the metastatic phenotype in colorectal cancer. A concatenated tandem array of consensus transcription factor (TF)-response elements was used to pull down nuclear extracts in two different pairs of colorectal cancer cells, KM12SM/KM12C and SW620/480, genetically related but differing in metastatic ability. Proteins were analyzed by label-free LC-MS and quantified with MaxLFQ. We found 240 proteins showing a significant dysregulation in highly metastatic KM12SM cells relative to nonmetastatic KM12C cells and 257 proteins in metastatic SW620 versus SW480...
November 21, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/29128291/detection-of-snps-of-t2dm-susceptibility-genes-by-a-ligase-detection-reaction-fluorescent-nanosphere-technique
#19
Yan Chen, Ying Zhao, Yan-Bo Li, Yan-Jun Wang, Gui-Zhen Zhang
OBJECTIVE: To establish a high throughput, low cost, and simple nanotechnology-based method for the detection of single nucleotide polymorphism (SNP) loci in type 2 diabetes mellitus (T2DM). METHODS: Multiplex ligase detection reaction (LDR) amplification was performed using fluorescently labeled magnetic nanosphere-bound upstream LDR probes and downstream probes labeled with a unique fluorescent group for each SNP locus. The amplified LDR products were separated by magnetic nanospheres and then scanned by fluorescence spectroscopy...
November 9, 2017: Analytical Biochemistry
https://www.readbyqxmd.com/read/29118424/methods-for-scarless-selection-free-generation-of-human-cells-and-allele-specific-functional-analysis-of-disease-associated-snps-and-variants-of-uncertain-significance
#20
Nicole B Coggins, Jacob Stultz, Henriette O'Geen, Luis G Carvajal-Carmona, David J Segal
With the continued emergence of risk loci from Genome-Wide Association studies and variants of uncertain significance identified from patient sequencing, better methods are required to translate these human genetic findings into improvements in public health. Here we combine CRISPR/Cas9 gene editing with an innovative high-throughput genotyping pipeline utilizing KASP (Kompetitive Allele-Specific PCR) genotyping technology to create scarless isogenic cell models of cancer variants in ~1 month. We successfully modeled two novel variants previously identified by our lab in the PALB2 gene in HEK239 cells, resulting in isogenic cells representing all three genotypes for both variants...
November 8, 2017: Scientific Reports
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