Functional Variants in the Promoter Region of Chitinase 3–Like 1 (CHI3L1) and Susceptibility to Schizophrenia Xinzhi Zhao, Ruqi Tang, Bo Gao, Yongyong.

Slides:

Advertisements

Similar presentations

TLR4 signal ablation attenuated neurological deficits by regulating microglial M1/M2 phenotype after traumatic brain injury in mice Xiaolong Yao, Shengwen.

Advertisements

Different signalling pathways regulate VEGF and IL-8 expression in breast cancer: implications for therapy Dina Chelouche-Lev, Claudia P. Miller, Carmen.

Repression of COUP-TFI Improves Bone Marrow-Derived Mesenchymal Stem Cell Differentiation into Insulin-Producing Cells Tao Zhang, Xiao-Hang Li, Dian-Bao.

Up-Regulation of Activating Transcription Factor-5 Suppresses SAP Expression to Activate T Cells in Hemophagocytic Syndrome Associated with Epstein-Barr.

Serotonin Transporter Promoter Gain-of-Function Genotypes Are Linked to Obsessive- Compulsive Disorder Xian-Zhang Hu, Robert H. Lipsky, Guanshan Zhu,

An IgE-associated polymorphism in STAT6 alters NF-κB binding, STAT6 promoter activity, and mRNA expression Michaela Schedel, PhD, Remo Frei, PhD, Christian.

Novel Functional Single Nucleotide Polymorphisms in the Latent Transforming Growth Factor-β Binding Protein-1L Promoter Tomomi Higashi, Satoru Kyo, Masaki.

Volume 134, Issue 4, Pages (April 2008)

Volume 11, Issue 6, Pages (June 2003)

Promoter and 3′-Untranslated-Region Haplotypes in the Vitamin D Receptor Gene Predispose to Osteoporotic Fracture: The Rotterdam Study Yue Fang, Joyce.

Volume 126, Issue 1, Pages (January 2004)

Impaired Activation of the Nrf2-ARE Signaling Pathway Undermines H2O2-Induced Oxidative Stress Response: A Possible Mechanism for Melanocyte Degeneration.

Volume 134, Issue 3, Pages e2 (March 2008)

Evaluation of clinical aspects and quality of life as risk factors for depression in patients with epilepsy Ting Zhao, Ming-yue Sun, Pei-min Yu, Guo-xing.

Volume 13, Issue 9, Pages (December 2015)

Intermittent cyclic mechanical tension promotes endplate cartilage degeneration via canonical Wnt signaling pathway and E-cadherin/β-catenin complex cross-talk

Molecular Therapy - Nucleic Acids

Down-regulation of CatSper1 channel in epididymal spermatozoa contributes to the pathogenesis of asthenozoospermia, whereas up-regulation of the channel.

Substance P Enhances the Production of Interferon-induced Protein of 10 kDa by Human Keratinocytes in Synergy with Interferon-γ Naoko Kanda, Shinichi.

Functional characterization of the atopy-associated gene PHF11

Genome-wide Association and Follow-Up Replication Studies Identified ADAMTS18 and TGFBR3 as Bone Mass Candidate Genes in Different Ethnic Groups Dong-Hai.

Mutation of a Nuclear Respiratory Factor 2 Binding Site in the 5′ Untranslated Region of the ADSL Gene in Three Patients with Adenylosuccinate Lyase Deficiency

ATM Gene Mutations Result in Both Recessive and Dominant Expression Phenotypes of Genes and MicroRNAs Denis A. Smirnov, Vivian G. Cheung The American.

Lipopolysaccharide activation of the MEK-ERK1/2 pathway in human monocytic cells mediates tissue factor and tumor necrosis factor α expression by inducing.

Volume 126, Issue 1, Pages (January 2004)

Serotonin Transporter Promoter Gain-of-Function Genotypes Are Linked to Obsessive- Compulsive Disorder Xian-Zhang Hu, Robert H. Lipsky, Guanshan Zhu,

Volume 136, Issue 5, Pages (May 2009)

IFN-γ Upregulates Expression of the Mouse Complement C1rA Gene in Keratinocytes via IFN-Regulatory Factor-1 Sung June Byun, Ik-Soo Jeon, Hyangkyu Lee,

Sp1 Is Required for Glucose-Induced Transcriptional Regulation of Mouse Vesicular Glutamate Transporter 2 Gene Tao Li, Liqun Bai, Jing Li, Suzu Igarashi,

A Nonsense Mutation in DHTKD1 Causes Charcot-Marie-Tooth Disease Type 2 in a Large Chinese Pedigree Wang-yang Xu, Ming-min Gu, Lian-hua Sun, Wen-ting.

Rose-Anne Romano, Barbara Birkaya, Satrajit Sinha

Volume 19, Issue 3, Pages (March 2017)

Nova2 Interacts with a Cis-Acting Polymorphism to Influence the Proportions of Drug- Responsive Splice Variants of SCN1A Erin L. Heinzen, Woohyun Yoon,

Volume 130, Issue 1, Pages (January 2006)

Susan M. Farrington, Juili Lin-Goerke, Jessica Ling, Yute Wang, John D

Regulation of α-Synuclein Expression by Poly (ADP Ribose) Polymerase-1 (PARP-1) Binding to the NACP-Rep1 Polymorphic Site Upstream of the SNCA Gene Ornit.

Integrative Functional Genomics Implicates EPB41 Dysregulation in Hepatocellular Carcinoma Risk Xinyu Yang, Dianke Yu, Yanli Ren, Jinyu Wei, Wenting.

Davina A. Lewis, Simone F. Hengeltraub, Feng C. Gao, Megan A

S100A15, an Antimicrobial Protein of the Skin: Regulation by E

17β-Estradiol Enhances the Production of Nerve Growth Factor in THP-1-Derived Macrophages or Peripheral Blood Monocyte-Derived Macrophages Naoko Kanda,

Volume 57, Issue 5, Pages (May 2000)

Identification and Functional Characterization of RSPO2 as a Susceptibility Gene for Ossification of the Posterior Longitudinal Ligament of the Spine

Naoko Kanda, Shinichi Watanabe Journal of Investigative Dermatology

A systems view of genetics in chronic kidney disease

MicroRNA Control in the Immune System: Basic Principles

Cyclooxygenase-2 Inhibitor Enhances Whereas Prostaglandin E2Inhibits the Production of Interferon-Induced Protein of 10 kDa in Epidermoid Carcinoma A431

Development of an Allele-Specific Real-Time PCR Assay for Discrimination and Quantification of p63 R279H Mutation in EEC Syndrome Vanessa Barbaro, Letizia.

Identification of the Transcriptional Targets of FOXP2, a Gene Linked to Speech and Language, in Developing Human Brain Elizabeth Spiteri, Genevieve.

Cowden Syndrome–Affected Patients with PTEN Promoter Mutations Demonstrate Abnormal Protein Translation Rosemary E. Teresi, Kevin M. Zbuk, Marcus G.

Volume 16, Issue 4, Pages (April 2015)

The G/G Genotype of a Resistin Single-Nucleotide Polymorphism at −420 Increases Type 2 Diabetes Mellitus Susceptibility by Inducing Promoter Activity.

Genome-wide Association Study Reveals Multiple Nasopharyngeal Carcinoma- Associated Loci within the HLA Region at Chromosome 6p21.3 Ka-Po Tse, Wen-Hui.

STAT proteins mediate angiotensin II–induced production of TIMP-1 in human proximal tubular epithelial cells Xiangmei Chen, Jianzhong Wang, Feng Zhou,

Repression of COUP-TFI Improves Bone Marrow-Derived Mesenchymal Stem Cell Differentiation into Insulin-Producing Cells Tao Zhang, Xiao-Hang Li, Dian-Bao.

ATM Gene Mutations Result in Both Recessive and Dominant Expression Phenotypes of Genes and MicroRNAs Denis A. Smirnov, Vivian G. Cheung The American.

Chondrogenic progenitor cells promote vascular endothelial growth factor expression through stromal-derived factor-1 S. Wang, C. Zhou, H. Zheng, Z. Zhang,

Volume 43, Issue 1, Pages (July 2011)

IFN-γ Represses IL-4 Expression via IRF-1 and IRF-2

Transcriptional Control of SLC26A4 Is Involved in Pendred Syndrome and Nonsyndromic Enlargement of Vestibular Aqueduct (DFNB4) Tao Yang, Hilmar Vidarsson,

Lawrence M. Pfeffer, Andrzej T. Slominski

Defining the Regulatory Elements in the Proximal Promoter of ΔNp63 in Keratinocytes: Potential Roles for Sp1/Sp3, NF-Y, and p63 Rose-Anne Romano, Barbara.

TNF Regulates the In Vivo Occupancy of Both Distal and Proximal Regulatory Regions of the MCP-1/JE Gene Dongsheng Ping, Peter L. Jones, Jeremy M. Boss

Naoko Kanda, Shinichi Watanabe Journal of Investigative Dermatology

Allele-specific transcription of the asthma-associated PHD finger protein 11 gene (PHF11) modulated by octamer-binding transcription factor 1 (Oct-1)

Bart A. Jessen, Marjorie A. Phillips, Robert H. Rice

Germline Mutations in CDH23, Encoding Cadherin-Related 23, Are Associated with Both Familial and Sporadic Pituitary Adenomas Qilin Zhang, Cheng Peng,

Bismarck Amoah-Apraku, Mao-Zhong Fang, Nicolas J. Guzman, M.D

Deon G. Uffort, Elizabeth A. Grimm, Julie A. Ellerhorst

Volume 129, Issue 2, Pages (August 2005)

HLA-C Level Is Regulated by a Polymorphic Oct1 Binding Site in the HLA-C Promoter Region Nicolas Vince, Hongchuan Li, Veron Ramsuran, Vivek Naranbhai,

Presentation transcript:

Functional Variants in the Promoter Region of Chitinase 3–Like 1 (CHI3L1) and Susceptibility to Schizophrenia Xinzhi Zhao, Ruqi Tang, Bo Gao, Yongyong Shi, Jian Zhou, Shengzhen Guo, Jing Zhang, Yabing Wang, Wei Tang, Junwei Meng, Sheng Li, Hongsheng Wang, Gang Ma, Chuwen Lin, Yue Xiao, Guoyin Feng, Zhiguang Lin, Shaomin Zhu, Yangling Xing, Hong Sang, David St. Clair, Lin He The American Journal of Human Genetics Volume 80, Issue 1, Pages 12-18 (January 2007) DOI: 10.1086/510438 Copyright © 2007 The American Society of Human Genetics Terms and Conditions

Figure 1 Genomic structure of CHI3L1 and the location of SNPs included in the present study. The American Journal of Human Genetics 2007 80, 12-18DOI: (10.1086/510438) Copyright © 2007 The American Society of Human Genetics Terms and Conditions

Figure 2 Luciferase reporter assay of SNP2, SNP3, and SNP4 common haplotypes in U251 cells. The transcriptional activity of the pCBG99 control was set at 100%. Each CHI3L1 haplotype was tested eight times. Among the haplotypes, the risk haplotype (CCC) revealed the lowest activity, whereas the protective haplotype (TTG) showed the highest activity (P=2.2×10−7, by one-way ANOVA). The American Journal of Human Genetics 2007 80, 12-18DOI: (10.1086/510438) Copyright © 2007 The American Society of Human Genetics Terms and Conditions

Figure 3 In vitro binding of U251 nuclear proteins to CHI3L1 promoter sequences containing SNP3 and SNP4. In lanes 1–4 and 9–10, probes of major alleles for each SNP were loaded. In lanes 5–8, probes of minor alleles for each SNP were loaded. Competitors are the unlabeled oligonucleotides with same allele as probes, and cross-competitors are the oligonucleotides with the other allele of probes. a, No obvious difference shown between the two alleles of SNP3. b, G-allele probes of SNP4 generating two binding complexes (lane 2), whereas C-allele probes generated one (lane 6). Loading 100× cross-competitors (C allele) does not eliminate the G-allele–specific band (lane 4). c, Supershift assay for the G-allele probes of SNP4 with use of antibodies of AP-2 and MYC. The presence of either of the antibodies resulted in a visible supershift band. The American Journal of Human Genetics 2007 80, 12-18DOI: (10.1086/510438) Copyright © 2007 The American Society of Human Genetics Terms and Conditions

Figure 4 Effect of inhibition of the MYC/MAX signaling pathways on CHI3L1 expression. In both cell lines, MYC-inhibitor trial severely reduces expression level of CHI3L1 (76% decreased in U251 and 82% decreased in THP-1). Double asterisk (**) indicates P<.01. The American Journal of Human Genetics 2007 80, 12-18DOI: (10.1086/510438) Copyright © 2007 The American Society of Human Genetics Terms and Conditions

Figure 5 Expression analyses of CHI3L1 in vivo. a, Expression level of CHI3L1 in the PBC from patients with schizophrenia and unaffected controls. The average level of CHI3L1 in unaffected controls was defined as 100. No significant difference in expression level between the two groups was detected (t test P=.081). b and c, Expression of CHI3L1 was associated with the genotype of both SNP4 (b) and SNP3 (c) in PBC (Kruskal-Wallis H test P<.01). d, Haplotypes in the promoter region of CHI3L1 associated with expression level of the gene in PBC. e, Relative allele-specific expression of the SNP5 data expressed as allele ratios of A/G. Patients who were heterozygotes for SNP4 revealed highly significant allele differences (t test P=9.1×10−6, corrected for 5 tests) f, Risperidone-treated mice did not change the mRNA level of CHI3L1 in blood and brain (t test P>.05). The expression level of CHI3L1 in untreated mice was defined as 100. The American Journal of Human Genetics 2007 80, 12-18DOI: (10.1086/510438) Copyright © 2007 The American Society of Human Genetics Terms and Conditions

Figure 6 Hypothetical scenario for CHI3L1 in the pathophysiology of schizophrenia. Impairment of AKT signaling and overactivation of immune responses were observed in the subjects with schizophrenia and were considered to contribute to the risk of schizophrenia. The CHI3L1 gene may partly compensate the alteration of the processes and, therefore, may play a role in preventing the progression of psychosis. The American Journal of Human Genetics 2007 80, 12-18DOI: (10.1086/510438) Copyright © 2007 The American Society of Human Genetics Terms and Conditions