The protein tyrosine phosphatase non-receptor 22 (PTPN22) R620W polymorphism has been related to susceptibility to autoimmune thyroid disease (AITD) with inconsistent results. Therefore, this meta-analysis was designed to assess a more accurate association between the PTPN22 R620W polymorphism and AITD susceptibility. A systematic search of the EMBASE, PubMed, Web of Science, CBM, CNKI, and WanFang databases was performed to determine relevant publications. Statistical analyses of the odds ratios (ORs), 95% confidence intervals (CIs), and values were performed using STATA software. Our meta-analysis included 18 separate studies comprised of 4,726 cases and 4,220 controls. In the allele and all genetic models, PTPN22 R620W polymorphism and Graves' disease (GD) (allele model TvsC: OR = 1.573; 95% CI = 1.378-1.795; < .001) and Hashimoto's thyroiditis (HT) (allele model TvsC: OR = 1.737; 95% CI = 1.230-2.454; = .002) susceptibility was positively associated. A racial subgroup analysis showed that the T allele significantly increased AITD susceptibility in all genetic models involving Caucasians, but not in Asians. This meta-analysis showed that the PTPN22 R620W polymorphism is associated with the risk of GD and HT in the overall study population. In addition, the PTPN22 R620W polymorphism is associated with elevated AITD risk in Caucasians, but not in Asians.
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http://dx.doi.org/10.1080/08820139.2020.1837154 | DOI Listing |
Free Radic Biol Med
December 2024
INSERM-U1149, CNRS-ERL8252, Université de Paris-Cité, Centre de Recherche sur l'Inflammation, Laboratoire d'Excellence Inflamex, DHU FIRE, Faculté de Médecine, Site Xavier Bichat, Paris, France. Electronic address:
Neutrophils are essential for host defense against infections, but they also play a key role in acute and chronic inflammation. The protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene encodes the lymphoid-specific tyrosine phosphatase (Lyp) and a genetic single-nucleotide polymorphism of PTPN22 rs2476601 (R620W) has been associated with several human autoimmune diseases, including rheumatoid arthritis (RA). Here, we investigated the role of Lyp in TNFα-induced priming of neutrophil ROS production and in the development of arthritis using new selective Lyp inhibitors.
View Article and Find Full Text PDFElife
March 2023
Department of Pediatrics and Immunology, University of Washington, Seattle, United States.
A genetic variant in the gene (R620W, rs2476601) is strongly associated with increased risk for multiple autoimmune diseases and linked to altered TCR regulation and T cell activation. Here, we utilize Crispr/Cas9 gene editing with donor DNA repair templates in human cord blood-derived, naive T cells to generate risk edited (620W), non-risk edited (620R), or knockout T cells from the same donor. risk edited cells exhibited increased activation marker expression following non-specific TCR engagement, findings that mimicked KO cells.
View Article and Find Full Text PDFSci Rep
April 2022
Department of Pharmacology, University of Minnesota, Minneapolis, MN, 55455, USA.
The kinase Csk is the primary negative regulator of the Src-family kinases (SFKs, e.g., Lck, Fyn, Lyn, Hck, Fgr, Blk, Yes), phosphorylating a tyrosine on the SFK C-terminal tail that mediates autoinhibition.
View Article and Find Full Text PDFFront Immunol
April 2022
Infectivology and Clinical Trials Research Department, Bambino Gesù Children's Hospital, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy.
Int J Mol Sci
December 2021
Infectivology and Clinical Trials Research Department, Bambino Gesù Children's Hospital, Scientific Institute for Research, Hospitalization and Healthcare (IRCCS), 00146 Rome, Italy.
Autoimmune endocrine disorders, such as type 1 diabetes (T1D) and thyroiditis, at present are treated with only hormone replacement therapy. This emphasizes the need to identify personalized effective immunotherapeutic strategies targeting T and B lymphocytes. Among the genetic variants associated with several autoimmune disorders, the C1858T polymorphism of the protein tyrosine phosphatase non-receptor type 22 () gene, encoding for Lyp variant R620W, affects the innate and adaptive immunity.
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