The Experts below are selected from a list of 519375 Experts worldwide ranked by ideXlab platform
Michael R. Erdos - One of the best experts on this subject based on the ideXlab platform.
-
association of Transcription Factor 7 like 2 tcf7l2 variants with type 2 diabetes in a finnish sample
Diabetes, 2006Co-Authors: Laura J. Scott, Lori L. Bonnycastle, Cristen J. Willer, Andrew G. Sprau, Anne U. Jackson, Narisu Narisu, William L. Duren, Peter S. Chines, Heather M. Stringham, Michael R. ErdosAbstract:Transcription Factor 7-like 2 ( TCF7L2 ) is part of the Wnt signaling pathway. Genetic variants within TCF7L2 on chromosome 10q were recently reported to be associated with type 2 diabetes in Icelandic, Danish, and American (U.S.) samples. We previously observed a modest logarithm of odds score of 0.61 on chromosome 10q, ∼1 Mb from TCF7L2 , in the Finland-United States Investigation of NIDDM Genetics study. We tested the five associated TCF7L2 single nucleotide polymorphism (SNP) variants in a Finnish sample of 1,151 type 2 diabetic patients and 953 control subjects. We confirmed the association with the same risk allele ( P value <0.05) for all five SNPs. Our strongest results were for rs12255372 (odds ratio [OR] 1.36 [95% CI 1.15–1.61], P = 0.00026) and rs7903146 (1.33 [1.14–1.56], P = 0.00042). Based on the CEU HapMap data, we selected and tested 12 additional SNPs to tag SNPs in linkage disequilibrium with rs12255372. None of these SNPs showed stronger evidence of association than rs12255372 or rs7903146 (OR ≤1.26, P ≥ 0.0054). Our results strengthen the evidence that one or more variants in TCF7L2 are associated with increased risk of type 2 diabetes.
-
Association of Transcription Factor 7-Like 2 (TCF7L2) Variants With Type 2 Diabetes in a Finnish Sample
Diabetes, 2006Co-Authors: Laura J. Scott, Lori L. Bonnycastle, Cristen J. Willer, Andrew G. Sprau, Anne U. Jackson, Narisu Narisu, William L. Duren, Peter S. Chines, Heather M. Stringham, Michael R. ErdosAbstract:Transcription Factor 7-like 2 ( TCF7L2 ) is part of the Wnt signaling pathway. Genetic variants within TCF7L2 on chromosome 10q were recently reported to be associated with type 2 diabetes in Icelandic, Danish, and American (U.S.) samples. We previously observed a modest logarithm of odds score of 0.61 on chromosome 10q, ∼1 Mb from TCF7L2 , in the Finland-United States Investigation of NIDDM Genetics study. We tested the five associated TCF7L2 single nucleotide polymorphism (SNP) variants in a Finnish sample of 1,151 type 2 diabetic patients and 953 control subjects. We confirmed the association with the same risk allele ( P value
Laura J. Scott - One of the best experts on this subject based on the ideXlab platform.
-
association of Transcription Factor 7 like 2 tcf7l2 variants with type 2 diabetes in a finnish sample
Diabetes, 2006Co-Authors: Laura J. Scott, Lori L. Bonnycastle, Cristen J. Willer, Andrew G. Sprau, Anne U. Jackson, Narisu Narisu, William L. Duren, Peter S. Chines, Heather M. Stringham, Michael R. ErdosAbstract:Transcription Factor 7-like 2 ( TCF7L2 ) is part of the Wnt signaling pathway. Genetic variants within TCF7L2 on chromosome 10q were recently reported to be associated with type 2 diabetes in Icelandic, Danish, and American (U.S.) samples. We previously observed a modest logarithm of odds score of 0.61 on chromosome 10q, ∼1 Mb from TCF7L2 , in the Finland-United States Investigation of NIDDM Genetics study. We tested the five associated TCF7L2 single nucleotide polymorphism (SNP) variants in a Finnish sample of 1,151 type 2 diabetic patients and 953 control subjects. We confirmed the association with the same risk allele ( P value <0.05) for all five SNPs. Our strongest results were for rs12255372 (odds ratio [OR] 1.36 [95% CI 1.15–1.61], P = 0.00026) and rs7903146 (1.33 [1.14–1.56], P = 0.00042). Based on the CEU HapMap data, we selected and tested 12 additional SNPs to tag SNPs in linkage disequilibrium with rs12255372. None of these SNPs showed stronger evidence of association than rs12255372 or rs7903146 (OR ≤1.26, P ≥ 0.0054). Our results strengthen the evidence that one or more variants in TCF7L2 are associated with increased risk of type 2 diabetes.
-
Association of Transcription Factor 7-Like 2 (TCF7L2) Variants With Type 2 Diabetes in a Finnish Sample
Diabetes, 2006Co-Authors: Laura J. Scott, Lori L. Bonnycastle, Cristen J. Willer, Andrew G. Sprau, Anne U. Jackson, Narisu Narisu, William L. Duren, Peter S. Chines, Heather M. Stringham, Michael R. ErdosAbstract:Transcription Factor 7-like 2 ( TCF7L2 ) is part of the Wnt signaling pathway. Genetic variants within TCF7L2 on chromosome 10q were recently reported to be associated with type 2 diabetes in Icelandic, Danish, and American (U.S.) samples. We previously observed a modest logarithm of odds score of 0.61 on chromosome 10q, ∼1 Mb from TCF7L2 , in the Finland-United States Investigation of NIDDM Genetics study. We tested the five associated TCF7L2 single nucleotide polymorphism (SNP) variants in a Finnish sample of 1,151 type 2 diabetic patients and 953 control subjects. We confirmed the association with the same risk allele ( P value
Wassim Y. Almawi - One of the best experts on this subject based on the ideXlab platform.
-
Transcription Factor-7-Like 2 Gene Variants Affect the Metabolic Phenotypes of Polycystic Ovary Syndrome.
Annals of nutrition & metabolism, 2015Co-Authors: Emily Gammoh, Naeema Mahmood, Samira Madan, Bashayer H. Ebrahim, Fekria E. Mustafa, Wassim Y. AlmawiAbstract:Background: Polycystic ovary syndrome (PCOS) is a common endocrinopathy, which shares genetic features with type 2 diabetes mellitus (T2DM). Insofar as Transcription Factor 7-like 2 (TCF7L2) is consistently replicated T2DM susceptibility locus, this study evaluates whether common TCF7L2 variants are associated with PCOS and related metabolic features. Methods: The association between TCF7L2 rs4506565, rs7903146, rs12243326, and rs12255372 SNPs and PCOS was tested in 242 women with PCOS and in 236 control women. Results: The allelic distribution of rs4506565, rs7903146, rs12243326, and rs12255372 TCF7L2 variants was not significantly different between women with PCOS and control women. The genotype distribution of the 4 TCF7L2 loci was comparable between PCOS cases and controls, irrespective of the genetic analysis model used (additive, dominant, recessive). Carriage of rs4506565 minor allele correlated with free insulin and homeostasis model assessment of insulin resistance, while the presence of rs12243326 and rs12255372 minor allele correlated with waist changes. Four-locus (rs4506565-rs7903146, rs12243326, and rs12255372) haplotype analysis identified PCOS-susceptible (ACTG) and -protective (TTTG) haplotypes, which remained significant after controlling for multiple comparisons and for key covariates. Conclusions: Although individual TCF7L2 variants were not associated with the presence of PCOS in Bahraini women, specific TCF7L2 haplotypes were identified, which were both positively and negatively associated with PCOS.
-
Polymorphisms of Transcription Factor-7-like 2 (TCF7L2) gene in Tunisian women with polycystic ovary syndrome (PCOS).
Gene, 2013Co-Authors: A. Ben-salem, Wassim Y. Almawi, M. Ajina, M. Suissi, H.s. Daher, Touhami MahjoubAbstract:Abstract Background and aims Polycystic ovary syndrome (PCOS) is a common endocrine disorder that affects women in their child-bearing age, and is often associated with insulin resistance and type 2 diabetes (T2DM). Given the overlap between PCOS and T2DM, we investigated the association of Transcription Factor-7-like 2 ( TCF7L2 ) variants rs4506565, rs7903146, rs12243326, and rs12255372 with the susceptibility to PCOS. Subjects and methods Study subjects comprised 119 Tunisian women with PCOS (mean age 29.8 ± 4.7 years), and 150 control women (mean age 30.6 ± 5.9 years). TCF7L2 genotyping was done by the allelic discrimination/real-time PCR method. Results Minor allele frequencies (MAFs) of rs4506565 ( P = 0.61), rs7903146 ( P = 0.68), rs12243326 ( P = 0.56), and rs12255372 ( P = 0.60) were comparable between PCOS cases and control subjects. As the four tested TCF7L2 variants were in linkage disequilibrium, 4-locus (rs4506565, rs7903146, rs12243326, rs12255372) haplotype analysis demonstrated that haplotype 2111 was initially negatively associated with PCOS [ P = 0.035; OR (95% CI) = 0.13 (0.02–0.85)], which was later lost upon correcting for multiple comparisons [ Pc = 0.248]. Conclusion Our data suggest that there is weak or no contribution of TCF7L2 gene polymorphism to PCOS in Tunisian women. Further studies with larger samples are necessary to confirm this observation.
-
Transcription Factor-7-like 2 gene variants are strongly associated with type 2 diabetes in Tunisian Arab subjects
Gene, 2012Co-Authors: Amira Turki, Touhami Mahjoub, Ghadeer S. Al-zaben, Nabil Mtiraoui, Hela Marmmuoch, Wassim Y. AlmawiAbstract:Abstract Genome-wide association studies validated Transcription Factor 7-like 2 ( TCF7L2 ) gene as confirmed type 2 diabetes (T2DM) susceptibility locus, and an ethnic contribution of TCF7L2 variants to T2DM risk was indicated. The aim of this study was to replicate in a Tunisian Arab population identified associations of common TCF7L2 variants with T2DM. We tested the association of TCF7L2 variants: rs4506565, rs7903146, rs12243326, and rs12255372, with T2DM in 900 Tunisian patients and 875 control subjects. TCF7L2 genotyping was done by allelic discrimination/real-time PCR method. Minor allele frequencies of rs4506565 ( P = 2.4 × 10 − 8 ), rs7903146 ( P = 1.2 × 10 − 6 ), rs12243326 ( P = 8.4 × 10 − 8 ) and rs12255372 ( P = 1.1 × 10 − 5 ) were significantly higher in cases. The four tested TCF7L2 variants were in linkage disequilibrium, and 4-locus (rs4506565, rs7903146, rs12243326, rs12255372) haplotype analysis demonstrated that haplotype 1111 was negatively associated ( Pc Pc = 0.008) and 2211 ( Pc = 0.020) were positively associated with T2DM risk, after controlling for a number of covariates. The strong contribution of TCF7L2 gene variants to T2DM among Tunisians is in line with similar findings in other ethnic groups, confirming TCF7L2 as a common T2DM candidate gene.
Ning Hou - One of the best experts on this subject based on the ideXlab platform.
-
Transcription Factor 7-like 2 Mediates Canonical Wnt/β-Catenin Signaling and c-Myc Upregulation in Heart Failure
Circulation. Heart failure, 2016Co-Authors: Ning Hou, Kenneth B. Margulies, Xuejun WangAbstract:Background— How canonical Wnt/β-catenin signals in adult hearts, especially in different diseased states, remains unclear. The proto-oncogene, c-Myc, is a Wnt target and an early response gene during cardiac stress. It is not clear whether c-Myc is activated or how it is regulated during heart failure. Methods and Results— We investigated canonical Wnt/β-catenin signaling and how it regulated c-Myc expression in failing hearts of human ischemic heart disease, idiopathic dilated cardiomyopathy, and murine desmin–related cardiomyopathy. Our data demonstrated that canonical Wnt/β-catenin signaling was activated through nuclear accumulation of β-catenin in idiopathic dilated cardiomyopathy, ischemic heart disease, and murine desmin–related cardiomyopathy when compared with nonfailing controls and Transcription Factor 7-like 2 (TCF7L2) was the main β-catenin partner of the T-cell Factor (TCF) family in adult hearts. We further revealed that c-Myc mRNA and protein levels were significantly elevated in failing hearts by real-time reverse Transcription polymerase chain reaction, Western blotting, and immunohistochemical staining. Immunoprecipitation and confocal microscopy further showed that β-catenin interacted and colocalized with TCF7L2. More importantly, chromatin immunoprecipitation confirmed that β-catenin and TCF7L2 were recruited to the regulatory elements of c-Myc. This recruitment was associated with increased histone H3 acetylation and Transcriptional upregulation of c-Myc. With lentiviral infection, TCF7L2 overexpression increased c-Myc expression and cardiomyocyte size, whereas shRNA-mediated knockdown of TCF7L2 suppressed c-Myc expression and cardiomyocyte growth in cultured neonatal rat cardiomyocytes. Conclusions— This study indicates that TCF7L2 mediates canonic Wnt/β-catenin signaling and c-Myc upregulation during abnormal cardiac remodeling in heart failure and suppression of Wnt/β-catenin to c-Myc axis can be explored for preventing and treating heart failure.
-
Transcription Factor 7 like 2 mediates canonical wnt β catenin signaling and c myc upregulation in heart failure
Circulation-heart Failure, 2016Co-Authors: Ning Hou, Kenneth B. Margulies, Xuejun WangAbstract:Background— How canonical Wnt/β-catenin signals in adult hearts, especially in different diseased states, remains unclear. The proto-oncogene, c-Myc, is a Wnt target and an early response gene during cardiac stress. It is not clear whether c-Myc is activated or how it is regulated during heart failure. Methods and Results— We investigated canonical Wnt/β-catenin signaling and how it regulated c-Myc expression in failing hearts of human ischemic heart disease, idiopathic dilated cardiomyopathy, and murine desmin–related cardiomyopathy. Our data demonstrated that canonical Wnt/β-catenin signaling was activated through nuclear accumulation of β-catenin in idiopathic dilated cardiomyopathy, ischemic heart disease, and murine desmin–related cardiomyopathy when compared with nonfailing controls and Transcription Factor 7-like 2 (TCF7L2) was the main β-catenin partner of the T-cell Factor (TCF) family in adult hearts. We further revealed that c-Myc mRNA and protein levels were significantly elevated in failing hearts by real-time reverse Transcription polymerase chain reaction, Western blotting, and immunohistochemical staining. Immunoprecipitation and confocal microscopy further showed that β-catenin interacted and colocalized with TCF7L2. More importantly, chromatin immunoprecipitation confirmed that β-catenin and TCF7L2 were recruited to the regulatory elements of c-Myc. This recruitment was associated with increased histone H3 acetylation and Transcriptional upregulation of c-Myc. With lentiviral infection, TCF7L2 overexpression increased c-Myc expression and cardiomyocyte size, whereas shRNA-mediated knockdown of TCF7L2 suppressed c-Myc expression and cardiomyocyte growth in cultured neonatal rat cardiomyocytes. Conclusions— This study indicates that TCF7L2 mediates canonic Wnt/β-catenin signaling and c-Myc upregulation during abnormal cardiac remodeling in heart failure and suppression of Wnt/β-catenin to c-Myc axis can be explored for preventing and treating heart failure.
Xuejun Wang - One of the best experts on this subject based on the ideXlab platform.
-
Transcription Factor 7-like 2 Mediates Canonical Wnt/β-Catenin Signaling and c-Myc Upregulation in Heart Failure
Circulation. Heart failure, 2016Co-Authors: Ning Hou, Kenneth B. Margulies, Xuejun WangAbstract:Background— How canonical Wnt/β-catenin signals in adult hearts, especially in different diseased states, remains unclear. The proto-oncogene, c-Myc, is a Wnt target and an early response gene during cardiac stress. It is not clear whether c-Myc is activated or how it is regulated during heart failure. Methods and Results— We investigated canonical Wnt/β-catenin signaling and how it regulated c-Myc expression in failing hearts of human ischemic heart disease, idiopathic dilated cardiomyopathy, and murine desmin–related cardiomyopathy. Our data demonstrated that canonical Wnt/β-catenin signaling was activated through nuclear accumulation of β-catenin in idiopathic dilated cardiomyopathy, ischemic heart disease, and murine desmin–related cardiomyopathy when compared with nonfailing controls and Transcription Factor 7-like 2 (TCF7L2) was the main β-catenin partner of the T-cell Factor (TCF) family in adult hearts. We further revealed that c-Myc mRNA and protein levels were significantly elevated in failing hearts by real-time reverse Transcription polymerase chain reaction, Western blotting, and immunohistochemical staining. Immunoprecipitation and confocal microscopy further showed that β-catenin interacted and colocalized with TCF7L2. More importantly, chromatin immunoprecipitation confirmed that β-catenin and TCF7L2 were recruited to the regulatory elements of c-Myc. This recruitment was associated with increased histone H3 acetylation and Transcriptional upregulation of c-Myc. With lentiviral infection, TCF7L2 overexpression increased c-Myc expression and cardiomyocyte size, whereas shRNA-mediated knockdown of TCF7L2 suppressed c-Myc expression and cardiomyocyte growth in cultured neonatal rat cardiomyocytes. Conclusions— This study indicates that TCF7L2 mediates canonic Wnt/β-catenin signaling and c-Myc upregulation during abnormal cardiac remodeling in heart failure and suppression of Wnt/β-catenin to c-Myc axis can be explored for preventing and treating heart failure.
-
Transcription Factor 7 like 2 mediates canonical wnt β catenin signaling and c myc upregulation in heart failure
Circulation-heart Failure, 2016Co-Authors: Ning Hou, Kenneth B. Margulies, Xuejun WangAbstract:Background— How canonical Wnt/β-catenin signals in adult hearts, especially in different diseased states, remains unclear. The proto-oncogene, c-Myc, is a Wnt target and an early response gene during cardiac stress. It is not clear whether c-Myc is activated or how it is regulated during heart failure. Methods and Results— We investigated canonical Wnt/β-catenin signaling and how it regulated c-Myc expression in failing hearts of human ischemic heart disease, idiopathic dilated cardiomyopathy, and murine desmin–related cardiomyopathy. Our data demonstrated that canonical Wnt/β-catenin signaling was activated through nuclear accumulation of β-catenin in idiopathic dilated cardiomyopathy, ischemic heart disease, and murine desmin–related cardiomyopathy when compared with nonfailing controls and Transcription Factor 7-like 2 (TCF7L2) was the main β-catenin partner of the T-cell Factor (TCF) family in adult hearts. We further revealed that c-Myc mRNA and protein levels were significantly elevated in failing hearts by real-time reverse Transcription polymerase chain reaction, Western blotting, and immunohistochemical staining. Immunoprecipitation and confocal microscopy further showed that β-catenin interacted and colocalized with TCF7L2. More importantly, chromatin immunoprecipitation confirmed that β-catenin and TCF7L2 were recruited to the regulatory elements of c-Myc. This recruitment was associated with increased histone H3 acetylation and Transcriptional upregulation of c-Myc. With lentiviral infection, TCF7L2 overexpression increased c-Myc expression and cardiomyocyte size, whereas shRNA-mediated knockdown of TCF7L2 suppressed c-Myc expression and cardiomyocyte growth in cultured neonatal rat cardiomyocytes. Conclusions— This study indicates that TCF7L2 mediates canonic Wnt/β-catenin signaling and c-Myc upregulation during abnormal cardiac remodeling in heart failure and suppression of Wnt/β-catenin to c-Myc axis can be explored for preventing and treating heart failure.