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Role of PTPN2/22 polymorphisms in pathophysiology of Crohn’s disease

AIM: To establish the relationship of protein tyrosine phosphatase non-receptor type 2 and 22 (PTPN2/22) polymorphisms and mycobacterial infections in Crohn’s disease (CD). METHODS: All 133 subjects’ blood samples were genotyped for nine single nucleotide polymorphisms (SNPs) in PTPN2/22 using TaqMa...

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Autores principales: Sharp, Robert C, Beg, Shazia A, Naser, Saleh A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Baishideng Publishing Group Inc 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5807669/
https://www.ncbi.nlm.nih.gov/pubmed/29456405
http://dx.doi.org/10.3748/wjg.v24.i6.657
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author Sharp, Robert C
Beg, Shazia A
Naser, Saleh A
author_facet Sharp, Robert C
Beg, Shazia A
Naser, Saleh A
author_sort Sharp, Robert C
collection PubMed
description AIM: To establish the relationship of protein tyrosine phosphatase non-receptor type 2 and 22 (PTPN2/22) polymorphisms and mycobacterial infections in Crohn’s disease (CD). METHODS: All 133 subjects’ blood samples were genotyped for nine single nucleotide polymorphisms (SNPs) in PTPN2/22 using TaqMan™ genotyping, while the effect of the SNPs on PTPN2/22 and IFN-γ gene expression was determined using RT-PCR. Detection of Mycobacterium avium subspecies paratuberculosis (MAP) IS900 gene was done by nPCR after DNA extraction from the isolated leukocytes of each subjects’ blood samples. T-cells isolated from the patient samples were tested for response to phytohematoagglutonin (PHA) mitogen or mycobacterial antigens by BrdU proliferation assays for T-cell activity. RESULTS: Out of the nine SNPs examined, subjects with either heterozygous (TC)/minor (CC) alleles in PTPN2:rs478582 occurred in 83% of CD subjects compared to 61% healthy controls (P-values < 0.05; OR = 3.03). Subjects with either heterozygous (GA)/minor (AA) alleles in PTPN22:rs2476601 occurred in 16% of CD compared to 6% healthy controls (OR = 2.7). Gene expression in PTPN2/22 in CD subjects was significantly decreased by 2 folds compared to healthy controls (P-values < 0.05). IFN-γ expression levels were found to be significantly increased by approxiately 2 folds in subjects when either heterozygous or minor alleles in PTPN2:rs478582 and/or PTPN22:rs2476601 were found (P-values < 0.05). MAP DNA was detected in 61% of CD compared to only 8% of healthy controls (P-values < 0.05, OR = 17.52), where subjects with either heterozygous or minor alleles in PTPN2:rs478582 and/or PTPN22:rs2476601 had more MAPbacteremia presence than subjects without SNPs did. The average T-cell proliferation in CD treated with PHA or mycobacteria antigens was, respectively, 1.3 folds and 1.5 folds higher than healthy controls without any significant SNP. CONCLUSION: The data suggests that SNPs in PTPN2/22 affect the negative regulation of the immune response in CD patients, thus leading to an increase in inflammation/apoptosis and susceptibility of mycobacteria.
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spelling pubmed-58076692018-02-17 Role of PTPN2/22 polymorphisms in pathophysiology of Crohn’s disease Sharp, Robert C Beg, Shazia A Naser, Saleh A World J Gastroenterol Basic Study AIM: To establish the relationship of protein tyrosine phosphatase non-receptor type 2 and 22 (PTPN2/22) polymorphisms and mycobacterial infections in Crohn’s disease (CD). METHODS: All 133 subjects’ blood samples were genotyped for nine single nucleotide polymorphisms (SNPs) in PTPN2/22 using TaqMan™ genotyping, while the effect of the SNPs on PTPN2/22 and IFN-γ gene expression was determined using RT-PCR. Detection of Mycobacterium avium subspecies paratuberculosis (MAP) IS900 gene was done by nPCR after DNA extraction from the isolated leukocytes of each subjects’ blood samples. T-cells isolated from the patient samples were tested for response to phytohematoagglutonin (PHA) mitogen or mycobacterial antigens by BrdU proliferation assays for T-cell activity. RESULTS: Out of the nine SNPs examined, subjects with either heterozygous (TC)/minor (CC) alleles in PTPN2:rs478582 occurred in 83% of CD subjects compared to 61% healthy controls (P-values < 0.05; OR = 3.03). Subjects with either heterozygous (GA)/minor (AA) alleles in PTPN22:rs2476601 occurred in 16% of CD compared to 6% healthy controls (OR = 2.7). Gene expression in PTPN2/22 in CD subjects was significantly decreased by 2 folds compared to healthy controls (P-values < 0.05). IFN-γ expression levels were found to be significantly increased by approxiately 2 folds in subjects when either heterozygous or minor alleles in PTPN2:rs478582 and/or PTPN22:rs2476601 were found (P-values < 0.05). MAP DNA was detected in 61% of CD compared to only 8% of healthy controls (P-values < 0.05, OR = 17.52), where subjects with either heterozygous or minor alleles in PTPN2:rs478582 and/or PTPN22:rs2476601 had more MAPbacteremia presence than subjects without SNPs did. The average T-cell proliferation in CD treated with PHA or mycobacteria antigens was, respectively, 1.3 folds and 1.5 folds higher than healthy controls without any significant SNP. CONCLUSION: The data suggests that SNPs in PTPN2/22 affect the negative regulation of the immune response in CD patients, thus leading to an increase in inflammation/apoptosis and susceptibility of mycobacteria. Baishideng Publishing Group Inc 2018-02-14 2018-02-14 /pmc/articles/PMC5807669/ /pubmed/29456405 http://dx.doi.org/10.3748/wjg.v24.i6.657 Text en ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved. http://creativecommons.org/licenses/by-nc/4.0/ This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial.
spellingShingle Basic Study
Sharp, Robert C
Beg, Shazia A
Naser, Saleh A
Role of PTPN2/22 polymorphisms in pathophysiology of Crohn’s disease
title Role of PTPN2/22 polymorphisms in pathophysiology of Crohn’s disease
title_full Role of PTPN2/22 polymorphisms in pathophysiology of Crohn’s disease
title_fullStr Role of PTPN2/22 polymorphisms in pathophysiology of Crohn’s disease
title_full_unstemmed Role of PTPN2/22 polymorphisms in pathophysiology of Crohn’s disease
title_short Role of PTPN2/22 polymorphisms in pathophysiology of Crohn’s disease
title_sort role of ptpn2/22 polymorphisms in pathophysiology of crohn’s disease
topic Basic Study
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5807669/
https://www.ncbi.nlm.nih.gov/pubmed/29456405
http://dx.doi.org/10.3748/wjg.v24.i6.657
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