Role Of Ptpn2/22 Polymorphisms In Pathophysiology Of Crohn'S Disease

Keywords

Crohn's disease; Mycobacteria; PTPN2; PTPN2/22; PTPN22; Single nucleotide polymorphisms

Abstract

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.

Publication Date

2-14-2018

Publication Title

World Journal of Gastroenterology

Volume

24

Issue

6

Number of Pages

657-670

Document Type

Article

Personal Identifier

scopus

DOI Link

https://doi.org/10.3748/wjg.v24.i6.657

Socpus ID

85041931257 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/85041931257

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