Investigation of IL23R, JAK2, and STAT3 gene polymorphisms and gene–gene interactions in Crohn’s disease and ulcerative colitis in a Turkish population

Can, Güray; Tezel, Ahmet; Gürkan, Hakan; Tozkır, Hilmi; Ünsal, Gülbin; Soylu, Ali Rıza; Umit, Hasan

doi:10.5152/tjg.2016.16327

Cited by 9 publications

(6 citation statements)

References 38 publications

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“…A meta-analysis was performed on 26 observational studies involving 8561 cases, which showed that the JAK2 haplotype GGCC_46/1 significantly raised the risk of development of MPNs and SVT [ 54 ]. Other evidence suggested a significant association between some SNPs included in the JAK2 haplotype GGCC_46/1 (e.g., rs10758669) and inflammatory disorders such as ulcerative colitis and Crohn's disease [ 55 , 56 , 57 ]. In this regard, it is known that the JAK2-STAT3 pathway is one of the most important cell signaling pathways in Crohn’s disease, being activated by the production of IL-6 and is responsible for the production of pro-inflammatory proteins [ 58 , 59 ].…”

Section: Clinical Implications Of the Jak2 46mentioning

confidence: 99%

The JAK2 GGCC (46/1) Haplotype in Myeloproliferative Neoplasms: Causal or Random?

Anelli

Zagaria

Specchia

et al. 2018

IJMS

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The germline JAK2 haplotype known as “GGCC or 46/1 haplotype” (haplotypeGGCC_46/1) consists of a combination of single nucleotide polymorphisms (SNPs) mapping in a region of about 250 kb, extending from the JAK2 intron 10 to the Insulin-like 4 (INLS4) gene. Four main SNPs (rs3780367, rs10974944, rs12343867, and rs1159782) generating a “GGCC” combination are more frequently indicated to represent the JAK2 haplotype. These SNPs are inherited together and are frequently associated with the onset of myeloproliferative neoplasms (MPN) positive for both JAK2 V617 and exon 12 mutations. The association between the JAK2 haplotypeGGCC_46/1 and mutations in other genes, such as thrombopoietin receptor (MPL) and calreticulin (CALR), or the association with triple negative MPN, is still controversial. This review provides an overview of the frequency and the role of the JAK2 haplotypeGGCC_46/1 in the pathogenesis of different myeloid neoplasms and describes the hypothetical mechanisms at the basis of the association with JAK2 gene mutations. Moreover, possible clinical implications are discussed, as different papers reported contrasting data about the correlation between the JAK2 haplotypeGGCC_46/1 and blood cell count, survival, or disease progression.

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Section: Clinical Implications Of the Jak2 46mentioning

confidence: 99%

The JAK2 GGCC (46/1) Haplotype in Myeloproliferative Neoplasms: Causal or Random?

Anelli

Zagaria

Specchia

et al. 2018

IJMS

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“…Surgery is not commonly required for CD patients; however, depending on disease severity and chronic relapse of inflammation, surgical removal of the inflamed tissues is needed in certain cases. Even though the carriage of STAT3 rs744166 risk “A” allele is relatively high in healthy individuals, which is 56.4% compared to 63.6% carriage in CD patients [26], it has been indicated in several studies that STAT3 rs744166 is associated with Crohn's disease susceptibility [18, 27]. Herein, we first genotyped our cohort of 94 CD patients and found that 87.2% of this cohort carried STAT3 rs744166 risk allele “A,” heterozygous or homozygous (Table 1).…”

Section: Resultsmentioning

confidence: 99%

STAT3 Genotypic Variant rs744166 and Increased Tyrosine Phosphorylation of STAT3 in IL-23 Responsive Innate Lymphoid Cells during Pathogenesis of Crohn’s Disease

Tang

Tan

Iqbal

et al. 2019

Journal of Immunology Research

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Crohn’s disease (CD) results from dysregulated immune responses to gut microbiota in genetically susceptible individuals, affecting multiple areas of the gastrointestinal tract. Innate lymphoid cells (ILCs) are tissue-resident innate effector lymphocytes which play crucial roles in mucosal immune defense, tissue repair, and maintenance of homeostasis. The accumulation of IFN-γ-producing ILC1s and increased level of proinflammatory cytokines produced by ILCs has been observed in the inflamed terminal ileum of CD patients. To date, the precise mechanisms of ILC plasticity and gene regulatory pathways in ILCs remain unclear. Signal transducer and activator of transcription 3 (STAT3) regulates gene expression in a cell-specific, cytokine-dependent manner, involving multiple immune responses. This study proposes the positive correlation between the prevalence of STAT3 rs744166 risky allele “A” with the severity of disease in a cohort of 94 CD patients. In addition, the results suggest an increased STAT3 activity in the inflamed ileum of CD patients, compared to unaffected ileum sections. Notably, IL-23 triggers the differentiation of CD117+NKp44- ILC3s and induces the activation of STAT3 in both CD117+NKp44- and CD117-NKp44- ILC subsets, implying the involvement of STAT3 in the initiation of ILC plasticity. Moreover, carriage of STAT3 “A” risk allele exhibited a higher basal level of STAT3 tyrosine phosphorylation, and an increased IL-23 triggered the pSTAT3 level. We also demonstrated that there was no delayed dephosphorylation of STAT3 in ILCs of both A/A and G/G donors. Overall, the results of this study suggest that IL-23-induced activation of STAT3 in the CD117-NKp44- ILC1s involves in ILC1-to-ILC3 plasticity and a potential regulatory role of ILC1 function. Those genetically susceptible individuals carried STAT3 rs744166 risky allele appear to have higher basal and cytokine-stimulated activation of STAT3 signal, leading to prolonged inflammation and chronic relapse.

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“…It is known that there may be regional variations in the prevalence of JAK2 V617F mutations depending on the population [19][20][21]. In a study performed by Can et al [22] in Turkey, JAK2 mutation was shown to be a factor in the cause of inflammatory bowel disease in the Turkish population.…”

Section: Discussionmentioning

confidence: 99%

An investigation of JAK2 mutation in patients with ulcerative colitis with a history of thrombosis

et al. 2023

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Background/Aim: JAK2 is a gene that provides instructions for making a protein called Janus kinase 2, which is involved in the signaling process that regulates the growth and division of cells. Variations in the JAK2 gene have been associated with several different diseases, including certain blood disorders like myeloproliferative neoplasms (MPNs) and ulcerative colitis (UC). The exact reason for ulcerative colitis is not fully understood. This study aimed to examine the possible role of JAK2 V617F mutation in the etiopathogenesis of ulcerative colitis. Methods: The included patients were selected with UC and with signs of thrombosis. The DNA isolation was carried out from peripheral blood for all included patients. RT-qPCR methods were used to find JAK2 V617F mutations in UC patients with signs of thrombosis. Results: 73.3% of the included patients in this study had 73.3% bloody diarrhea and 80% had abdominal pain. Also, the JAK2 V617F mutation rate was detected in 6.6 % of the patients included in the study. Conclusion: In this study, it was found that the V617F mutation was relatively rare in ulcerative colitis patients and there was no correlation with the JAK2 V617F mutation in most of the ulcerative colitis cases with thrombotic symptoms.

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Investigation of IL23R, JAK2, and STAT3 gene polymorphisms and gene–gene interactions in Crohn’s disease and ulcerative colitis in a Turkish population

Cited by 9 publications

References 38 publications

The JAK2 GGCC (46/1) Haplotype in Myeloproliferative Neoplasms: Causal or Random?

The JAK2 GGCC (46/1) Haplotype in Myeloproliferative Neoplasms: Causal or Random?

STAT3 Genotypic Variant rs744166 and Increased Tyrosine Phosphorylation of STAT3 in IL-23 Responsive Innate Lymphoid Cells during Pathogenesis of Crohn’s Disease

An investigation of JAK2 mutation in patients with ulcerative colitis with a history of thrombosis

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