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https://www.readbyqxmd.com/read/28646072/genetic-and-environmental-interactions-modify-the-risk-of-diabetes-related-autoimmunity-by-6-years-of-age-the-teddy-study
#1
Jeffrey P Krischer, Kristian F Lynch, Åke Lernmark, William A Hagopian, Marian J Rewers, Jin-Xiong She, Jorma Toppari, Anette-G Ziegler, Beena Akolkar
OBJECTIVE: We tested the associations between genetic background and selected environmental exposures with respect to islet autoantibodies and type 1 diabetes. RESEARCH DESIGN AND METHODS: Infants with HLA-DR high-risk genotypes were prospectively followed for diabetes-related autoantibodies. SNPs came from the Illumina ImmunoChip and environmental exposure data were by parental report. Children were followed to age 6 years. RESULTS: Insulin autoantibodies occurred earlier than GAD antibody (GADA) and then declined, while GADA incidence rose and remained constant (significant in HLA-DR4 but not in the DR3/3 children)...
June 23, 2017: Diabetes Care
https://www.readbyqxmd.com/read/28627089/analysis-of-ptpn22-zfat-and-myo9b-polymorphisms-in-turner-syndrome-and-risk-of-autoimmune-disease
#2
E Villanueva-Ortega, B Ahedo, M A Fonseca-Sánchez, J Pérez-Durán, N Garibay-Nieto, M T Macías-Galavíz, Y Trujillo-Cabrera, E García-Latorre, G Queipo
Turner syndrome (TS) is one of the most common sexual chromosome abnormalities and is clearly associated with an increased risk of autoimmune diseases, particularly thyroid disease and coeliac disease (CD). Single-nucleotide polymorphism analyses have been shown to provide correlative evidence that specific genes are associated with autoimmune disease. Our aim was to study the functional polymorphic variants of PTPN22 and ZFAT in relation to thyroid disease and those of MYO9B in relation to CD. A cross-sectional comparative analysis was performed on Mexican mestizo patients with TS and age-matched healthy females...
June 18, 2017: International Journal of Immunogenetics
https://www.readbyqxmd.com/read/28619073/genome-wide-pathway-analysis-identifies-vegf-pathway-association-with-oral-ulceration-in-systemic-lupus-erythematosus
#3
Adrià Aterido, Antonio Julià, Patricia Carreira, Ricardo Blanco, José Javier López-Longo, José Javier Pérez Venegas, Àlex Olivé, José Luís Andreu, Maria Ángeles Aguirre-Zamorano, Paloma Vela, Joan M Nolla, José Luís Marenco-de la Fuente, Antonio Zea, José María Pego, Mercedes Freire, Elvira Díez, María López-Lasanta, Mireia López-Corbeto, Núria Palau, Raül Tortosa, Josep Lluís Gelpí, Devin Absher, Richard M Myers, Antonio Fernández-Nebro, Sara Marsal
BACKGROUND: Systemic lupus erythematosus (SLE) is a genetically complex rheumatic disease characterized by heterogeneous clinical manifestations of unknown etiology. Recent studies have suggested the existence of a genetic basis for SLE heterogeneity. The objective of the present study was to identify new genetic variation associated with the clinically relevant phenotypes in SLE. METHODS: A two-stage pathway-based approach was used to identify the genetic variation associated with the main clinical phenotypes in SLE...
June 15, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28615512/hdac10-promotes-angiogenesis-in-endothelial-cells-through-the-ptpn22-erk-axis
#4
Baoyu Duan, Dan Ye, Songcheng Zhu, Wenwen Jia, Chenqi Lu, Guiying Wang, Xudong Guo, Yangyang Yu, Chuanyue Wu, Jiuhong Kang
Angiogenesis is crucially involved in many physiological and pathological processes including tumor growth, but the molecular mechanisms regulating angiogenesis are incompletely understood. In this study, we investigated the functions and mechanism of histone deacetylase 10 (HDAC10), a member of the HDAC II family, in regulation of angiogenesis. HDAC10 overexpression in human umbilical vein endothelial cells (HUVECs) promoted tube formation, whereas depletion of HDAC10 from HUVECs inhibited tube formation in vitro and in vivo...
May 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28603863/identification-of-ptpn22-st6gal1-and-jazf1-as-psoriasis-risk-genes-demonstrates-shared-pathogenesis-between-psoriasis-and-diabetes
#5
Honglei Wang, Zhenzhen Wang, Parimi Leela Rani, Xi'an Fu, Wenjun Yu, Fangfang Bao, Gongqi Yu, Jianke Li, Lulu Li, Lele Sun, Zhenhua Yue, Qing Zhao, Qing Pan, Jing Cao, Chuan Wang, Xiaojun Chi, Yaru Wang, Qing Yang, Zihao Mi, Hong Liu, Furen Zhang
The biological connections between psoriasis and diabetes have been suggested by epidemiological, immunological and genetic studies. To identify additional shared susceptibility loci and investigate shared pathogenesis between these two diseases, we genotyped 89 reported diabetes susceptibility loci in 4,456 psoriasis cases and 6,027 controls of Chinese population using the MassARRAY system from Sequenom. We discovered three significant associations at rs6679677 on 1p13.2 (P = 6.15 × 10(-5) , OR = 5.07), rs16861329 on 3q27...
June 12, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28568286/rnaset2-gpr174-and-ptpn22-gene-polymorphisms-are-related-to-the-risk-of-liver-damage-associated-with-the-hyperthyroidism-in-patients-with-graves-disease
#6
Qing Zhang, Shaozheng Liu, Yanxing Guan, Qingjie Chen, Qing Zhang, Xiang Min
OBJECTIVES: This study was designed to unveil the association of GPR174 rs3827440, PTPN22 rs3789604, and RNASET2 rs9355610 with the onset of liver damage (LD) among the Graves' disease (GD) patients. METHODS: A total of 120 GD patients were divided into the none-LD and LD groups. Several indicators were detected for assessing liver functions, and genotypes of single nucleotide polymorphisms (SNPs) were identified. Logistic regression was introduced for investigating the relationship between risk SNPs and LD-associated hyperthyroidism in GD patients...
May 31, 2017: Journal of Clinical Laboratory Analysis
https://www.readbyqxmd.com/read/28555069/association-between-protein-tyrosine-phosphatase-non-receptor-type-22-ptpn22-polymorphisms-and-risk-of-ankylosing-spondylitis-a-meta-analysis
#7
Weiming Wang, Xiantao Meng, Yupeng Liu, Xiaojun Ma, Qian Zhang, Chunhui Li, Chenye Li, Liubao Ren
BACKGROUND Ankylosing spondylitis (AS) is a chronic autoimmune disease that involves the imbalance of peripheral tolerance possibly caused by the negative signal of activated T cells. The polymorphisms in the human protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene have been pointed out to be related to the pathogenesis of AS, but conclusions over this issue remain contradictory. We attempted to give a more precise conclusion about the effects of PTPN22 polymorphisms on AS risk by means of a meta-analysis...
May 30, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28545409/genetic-variation-and-expression-levels-of-tight-junction-genes-identifies-association-between-magi3-and-inflammatory-bowel-disease
#8
Elisabeth Norén, Sven Almer, Jan Söderman
BACKGROUND: Inflammatory bowel disease (IBD) is associated with increased intestinal permeability, which involves paracellular passage regulated through tight junctions (TJ). The aim of the study was to investigate single nucleotide polymorphisms (SNP) located in genes encoding interacting TJ proteins and corresponding expressions, in relation to IBD. METHODS: Allelic associations between TJ-related genes (F11R, MAGI1, MAGI2, MAGI3, PARD3, PTEN, and TJP1) and IBD, Crohn's disease (CD), or ulcerative colitis (UC) were investigated...
May 25, 2017: BMC Gastroenterology
https://www.readbyqxmd.com/read/28537236/-allelic-variants-of-immune-response-genes-in-children-with-infectious-complications-during-the-treatment-of-acute-leukemia
#9
M A Avdonina, I S Abramov, Y I Ammour, T V Nasedkina
Infectious complications that arise during the treatment of children with acute leukemia with chemotherapeutic agents at high doses represent a serious problem in oncohematology. To find genetic conditions that may lead to the development of postchemotherapy infections, the genomes of 12 children with acute leukemia who had severe infectious complications during therapy were examined. At the same time, the coding regions of 17 genes involved in the regulation of the immune response were determined by massive parallel sequencing...
March 2017: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/28528372/associations-between-ptpn22-and-tlr9-polymorphisms-and-systemic-lupus-erythematosus-a-comprehensive-meta-analysis
#10
Li-Ya Hu, Zhi Cheng, Bo Zhang, Qiong Yin, Xiao-Wei Zhu, Pian-Pian Zhao, Ming-Yu Han, Xiao-Bo Wang, Hou-Feng Zheng
Previous studies have explored the relationship of PTPN22 and TLR9 polymorphisms with systemic lupus erythematosus (SLE). In consideration of the population stratification, conflicting results and updating data, we conducted a comprehensive meta-analysis, which consists of a total of 17 research articles (9120 cases and 11,724 controls) for PTPN22 and 20 articles (including up to 2808 cases and 3386 controls) for TLR9. Significant association was verified between PTPN22 rs2476601 and SLE in the overall population (OR = 1...
May 20, 2017: Archives of Dermatological Research
https://www.readbyqxmd.com/read/28527290/association-of-polymorphic-variants-of-ptpn22-tnf-and-vdr-genes-in-children-with-lupus-nephritis-a-study-in-colombian-family-triads
#11
Gloria Garavito, Eduardo Egea, Luis Fang, Clara Malagón, Carlos Olmos, Luz González, Pilar Guarnizo, Gustavo Aroca, Guillermo López, Antonio Iglesias
INTRODUCTION: Systemic lupus erythematosus is an autoimmune disease in which the severity varies according to race, sex and age of onset. This variation is also observed in the genetic markers associated with the disease, including PTPN22, VDR and TNF genes. The genetic stratification in different populations worldwide can influence the variability. OBJECTIVE: To analyze the heritability of PTPN22, VDR and TNF genetic variants and their association with pediatric lupus nephritis in Colombian families...
June 1, 2017: Biomédica: Revista del Instituto Nacional de Salud
https://www.readbyqxmd.com/read/28522807/traf3-enhances-tcr-signaling-by-regulating-the-inhibitors-csk-and-ptpn22
#12
Alicia M Wallis, Ellie C Wallace, Bruce S Hostager, Zuoan Yi, Jon C D Houtman, Gail A Bishop
The adaptor protein TNF receptor associated factor (TRAF) 3 is required for effective TCR signaling and normal T cell effector functions, and associates with the CD3/CD28 complex upon activation. To determine how TRAF3 promotes proximal TCR signaling, we studied TRAF3-deficient mouse and human T cells, which showed a marked reduction in activating phosphorylation of the TCR-associated kinase Lck. The impact of TRAF3 on this very early signaling event led to the hypothesis that TRAF3 restrains one or both of two known inhibitors of Lck, C-terminal Src kinase (Csk) and protein tyrosine phosphatase N22 (PTPN22)...
May 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28504962/association-of-stat4-and-ptpn22-polymorphisms-and-their-interactions-with-type-1-autoimmune-hepatitis-susceptibility-in-chinese-han-children
#13
Xiaofeng Li, Huiqin Chen, Yun Cai, Pingping Zhang, Zhuanggui Chen
AIMS: To investigate the impact of signal transducer and activator of transcription 4 (STAT4) and the protein tyrosine phosphatase N22 (PTPN22) gene single nucleotide polymorphisms (SNPs), gene- gene interactions and haplotype on type-1 Autoimmune Hepatitis (AIH) risk. RESULTS: Logistic regression analysis showed that type 1 AIH was significantly higher in carriers of T allele of rs7574865 than those with GG genotype (P- value less than 0.001), higher in carriers of C allele of rs7582694 than those with GG genotype (P- value < 0...
April 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28500376/the-ptpn22-r263q-polymorphism-confers-protection-against-systemic-lupus-erythematosus-and-rheumatoid-arthritis-while-ptpn22-r620w-confers-susceptibility-to-graves-disease-in-a-mexican-population
#14
Daniela Josabeth López-Cano, Daniel Cadena-Sandoval, Olga Beltrán-Ramírez, Rosa Elda Barbosa-Cobos, Fausto Sánchez-Muñoz, Luis Manuel Amezcua-Guerra, Yaneli Juárez-Vicuña, María Concepción Aguilera-Cartas, José Moreno, Jesús Bautista-Olvera, Guillermo Valencia-Pacheco, Ricardo F López-Villanueva, Julian Ramírez-Bello
OBJECTIVE: The functional PTPN22 R620W polymorphism (rs2476601) is clearly associated with susceptibility to several autoimmune diseases (ADs). However, the PTPN22 R263Q polymorphism (rs33996649) has been scarcely explored in different ADs. Here we aimed to examine the associations of the PTPN22 R620W and R263Q polymorphisms with susceptibility to or protection against rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Graves' disease (GD) among Mexican patients. METHODS: We conducted a case-control study including 876 patients (405 with SLE, 388 with RA, and 83 with GD) and 336 healthy control individuals...
May 12, 2017: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/28481156/association-of-ptpn22-single-nucleotide-polymorphisms-with-celiac-disease
#15
Majid Aflatounian, Arezou Rezaei, Maryam Sadr, Amene Saghazadeh, Nazanin Elhamian, Hengameh Sadeghi, Fatemeh Motevasselian, Fatemeh Farahmand, Gholamhossein Fallahi, Farzaneh Motamed, Mehri Najafi, Nima Rezaei
OBJECTIVES: Celiac disease is a chronic autoimmune disease in which gene-environment interactions cause the immune system to unfavorably react to naturally gluten-containing foods. PTPN22 plays a crucial role in regulating the function of various cells of the immune system, particularly T cells. Polymorphisms of the PTPN22 gene have been associated with many autoimmune diseases. The present genetic association study was conducted to investigate the possible associations between PTPNTT single nucleotide polymorphisms (SNPs) and celiac disease in an Iranian population...
June 2017: Fetal and Pediatric Pathology
https://www.readbyqxmd.com/read/28444099/association-of-the-protein-tyrosine-phosphatase-non-receptor-22-polymorphism-ptpn22-with-endometriosis-a-meta-analysis
#16
Noel Pabalan, Hamdi Jarjanazi, Denise Maria Christofolini, Bianca Bianco, Caio Parente Barbosa
Objective: To evaluate PTPN22 C1858T polymorphism and the risk of endometriosis. Methods: A meta-analysis of 10 published case-control studies (from four articles), with a total sample of 971 cases and 1,181 controls, was performed. We estimated risk (odds ratio and 95% confidence intervals) of endometriosis associations with the C1858T polymorphism. Results: A significant increased risk in all genetic models of the variant T allele with endometriosis (odds ratio: 3...
January 2017: Einstein
https://www.readbyqxmd.com/read/28439269/genome-wide-identification-of-target-genes-for-the-key-b-cell-transcription-factor-ets1
#17
Prontip Saelee, Alyssa Kearly, Stephen L Nutt, Lee Ann Garrett-Sinha
BACKGROUND: The transcription factor Ets1 is highly expressed in B lymphocytes. Loss of Ets1 leads to premature B cell differentiation into antibody-secreting cells (ASCs), secretion of autoantibodies, and development of autoimmune disease. Despite the importance of Ets1 in B cell biology, few Ets1 target genes are known in these cells. RESULTS: To obtain a more complete picture of the function of Ets1 in regulating B cell differentiation, we performed Ets1 ChIP-seq in primary mouse B cells to identify >10,000-binding sites, many of which were localized near genes that play important roles in B cell activation and differentiation...
2017: Frontiers in Immunology
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
#18
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/28437437/use-of-short-interfering-rna-delivered-by-cationic-liposomes-to-enable-efficient-down-regulation-of-ptpn22-gene-in-human-t-lymphocytes
#19
Valentina Perri, Marsha Pellegrino, Francesca Ceccacci, Anita Scipioni, Stefania Petrini, Elena Gianchecchi, Anna Lo Russo, Serena De Santis, Giovanna Mancini, Alessandra Fierabracci
Type 1 diabetes and thyroid disease are T cell-dependent autoimmune endocrinopathies. The standard substitutive administration of the deficient hormones does not halt the autoimmune process; therefore, development of immunotherapies aiming to preserve the residual hormonal cells, is of crucial importance. PTPN22 C1858T mutation encoding for the R620W lymphoid tyrosine phosphatase variant, plays a potential pathophysiological role in autoimmunity. The PTPN22 encoded protein Lyp is a negative regulator of T cell antigen receptor signaling; R620W variant, leading to a gain of function with paradoxical reduced T cell activation, may represent a valid therapeutic target...
2017: PloS One
https://www.readbyqxmd.com/read/28430763/protective-effect-of-pinitol-against-inflammatory-mediators-of-rheumatoid-arthritis-via-inhibition-of-protein-tyrosine-phosphatase-non-receptor-type-22-ptpn22
#20
Kewen Zheng, Zhixuan Zhao, Na Lin, Yiyan Wu, Ying Xu, Wanli Zhang
BACKGROUND The aim of the current study was to explore the anti-arthritic effect of pinitol via assessing its effect on various inflammatory mediators and its possible mechanism of action. MATERIAL AND METHODS We assessed the anti-arthritic effect of pinitol in a formaldehyde- and CFA-induced arthritic model in Wistar Swiss albino strain rats divided into 6 groups. The rats received different doses of pinitol and indomethacin for 28 days. The arthritic index and body weight were determined at regular intervals, together with hepatic, hematological, and antioxidant parameters...
April 21, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
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