Single-nucleotide variants in TGFB1, TGFBR2, IL17A, and IL17F immune response genes contribute to follicular lymphoma susceptibility and aggressiveness.
Ontology highlight
ABSTRACT:
SUBMITTER: Assis-Mendonca GR
PROVIDER: S-EPMC7538580 | biostudies-literature | 2020 Oct
REPOSITORIES: biostudies-literature
Publications
Single-nucleotide variants in TGFB1, TGFBR2, IL17A, and IL17F immune response genes contribute to follicular lymphoma susceptibility and aggressiveness.
Assis-Mendonça Guilherme Rossi GR Lourenço Gustavo Jacob GJ Delamain Márcia Torresan MT de Lima Vladmir Cláudio Cordeiro VCC Colleoni Gisele Wally Braga GWB de Souza Cármino Antônio CA Soares Fernando Augusto FA Lima Carmen Silvia Passos CSP Vassallo José J
Blood cancer journal 20201006 10
Similar Datasets
Project description: Not available
| S-EPMC1798089 | biostudies-literature
Project description:BackgroundInterleukin-17 plays important role in the pathogenesis of rheumatoid arthritis (RA). The aim of this study was to examine the associations between polymorphisms in the IL17A and IL17F genes and RA.MethodsWe examined 422 RA patients and 337 subjects as a control group. Single nucleotide polymorphism (SNP) in the IL17A (rs2275913) and IL17F (rs763780, rs11465553, rs2397084) genes were genotyped using TaqMan genotyping assays from Life Technologies Genomic.ResultsThere were no significant differences in distribution of IL17A and IL17F genotypes and alleles between RA patients and control group. There were no significant associations between IL17A and IL17F genotypes and age of disease diagnosis rheumatoid factor, erosive disease as well as extra-articular manifestations.ConclusionsThe results of this study suggest, that IL17A and IL17F gene polymorphism are not the important factors associated with susceptibility and some clinical parameters of RA in a Polish population.
| S-EPMC4864924 | biostudies-literature
Project description:IL23/IL17 pathway plays an important role in the development of inflammatory bowel diseases (IBD). In general, the genes encoding the cytokines are genetically polymorphic and polymorphisms in genes IL23R and IL17 have been proved to be associated with its susceptibility to inflammatory diseases as well as cancer including colorectal cancer. Moreover, it has been shown that these interleukins are involved in anti-tumor or pro-tumor effects of various cancers. Previously, we showed that there is a significant association between IL17A, IL17F and IL23R polymorphisms as well as the occurrence of colorectal cancer and the clinical features of the disease. The purpose of the present work is to investigate an association between IL17A, IL17F and IL23R polymorphisms in 102 Tunisian patients with colorectal cancer treatment. The association was analyzed by statistical tools. We found that patients with mutated genotypes of IL17A G197A SNP could be a risk factor for the inefficiency of chemotherapy and radiotherapy. Unlike IL17F variant, patients with wild type genotypes require surgery and adjuvant chemotherapy. On the one hand, we found no evidence that supports a significant association between IL23R polymorphism and the combined genotypes of these three genes and the colorectal cancer treatment. On the other hand, we showed that there is an important interaction between IL17A/IL17F polymorphisms and the stage of the disease as well as its treatment. Finally, patients with IL17F wild type genotype highlighted that there is a valid longer OS without all treatments and with radiotherapy and a neoadjuvant chemotherapy. In contrast, we observed that there are no relationships between IL17A, IL23R and the survival of these patients neither with nor without the treatment. Our results suggest that polymorphisms in IL17A and IL17F genes may be a predictive source of colorectal cancer therapy type. Therefore, IL17F may serve as an independent prognostic factor for overall survival in patients with colorectal cancer.
| S-EPMC4470506 | biostudies-literature
Project description:BackgroundInterleukin 17 is a proinflammatory cytokine involved in immune response after allograft transplantation. IL-17 family of proinflammatory cytokines includes IL-17A and IL-17F. Previous studies have demonstrated that the rs2275913 IL17A and the rs11465553 IL17F gene polymorphism are associated with kidney allograft function. Because of the association between these polymorphisms and post-transplant immune response, we assume that these single nucleotide polymorphisms may affect morphological structure of transplanted kidney. The aim of this study was to examine the association of rs2275913 IL17A and rs2397084, rs11465553 and rs763780 IL17F gene polymorphisms with histopathological changes in transplanted kidney biopsies such as: glomerulitis, tubulitis, arteritis, cell infilitration and fibrosis.MethodsThe study enrolled 82 patients after renal graft transplantation in whom a kidney biopsy was performed because of impaired graft function. The rs2397084 T > C (Glu126Gly), rs11465553 G > A (Val155Ile) and rs763780 T > C (His167Arg) polymorphisms within the IL17F gene and the rs2275913 A > G (- 197 A > G) polymorphism within the IL17A gene promoter were genotyped using TaqMan genotyping assays on a 7500 FAST Real-Time PCR System (Applied Biosystems, USA).ResultsThere was a significant association between the rs2275913 IL17A gene polymorphism and the grade of tubulitis, which was more severe among patients with the A allele, compared to recipients with the GG genotype (GG vs. AG + AA, P = 0.02), and with the grade of arteriolar hyaline thickening and mesangial matrix increase, which were more severe among patients with the G allele compared to recipients with the AA genotype (AA vs. AG + GG, P = 0.01 and P = 0.04, respectively). Tubular atrophy and interstitial fibrosis were more severe among individuals with the C allele at the rs763780 IL17F gene polymorphism (TT vs. TC, P = 0.09 and P = 0.017, respectively). However, it should be taken into account that the statistical significance was achieved without correction for multiple testing, and no significant association would remain significant after such correction.ConclusionsThe results of this study may suggest a possible association between the rs2275913 IL17A and rs2275913 IL17A gene polymorphisms and some histopathological changes in transplanted kidney biopsies.
| S-EPMC6454731 | biostudies-literature
Project description:We conducted genome-wide association studies of non-Hodgkin lymphoma using Illumina HumanHap550 BeadChips to identify subtype-specific associations in follicular, diffuse large B-cell and chronic lymphocytic leukemia/small lymphocytic lymphomas. We found that rs6457327 on 6p21.33 was associated with susceptibility to follicular lymphoma (FL; N = 189 cases, 592 controls) with validation in another 456 FL cases and 2,785 controls (combined allelic P = 4.7 x 10(-11)). The region of strongest association overlapped C6orf15 (STG), located near psoriasis susceptibility region 1 (PSORS1).
| S-EPMC2823809 | biostudies-other
Project description:Prostaglandin E2 (PGE2), IL-23 and IL-1β are implicated in inflammatory bowel disease susceptibility, likely in part by modulating IL-17 producing CD4(+) T helper (Th17) cells. To better understand how these three mediators affect Th17 cell memory responses, we characterized the gene expression profiles of activated human peripheral CD4(+) effector memory T cells and sorted Th17 memory cells from healthy donors concurrent with IL17A mRNA induction mediated by PGE2 and/or IL-23 plus IL-1β. We discovered that PGE2 and IL-23 plus IL-1β differentially regulate Th17 cytokine expression and synergize to induce IL-17A, but not IL-17F. IL-23 plus IL-1β preferentially induce IL-17F expression. The addition of PGE2 to IL-23 plus IL-1β only enhances IL-17A expression as mediated by the PGE2 EP4 receptor, and promotes a switch from an IL-17F to an IL-17A predominant immune response. The human Th17 HuT-102 cell line was also found to constitutively express IL-17A, but not IL-17F. We went on to show that the IL17A and IL17F loci have divergent epigenetic architectures in unstimulated HuT-102 and primary Th17 cells and are poised for preferential expression of IL17A. We conclude that the chromatin for IL17A and IL17F are distinctly regulated, which may play an important role in mucosal health and disease.
| S-EPMC3770803 | biostudies-literature
Project description:Th17 lymphocytes, that produce IL17A, IL17F, and IL22, play a crucial role during the immune response against Mycobacterium tuberculosis (Mtb) infection. Whereas, the contribution of IL17A in immunity to tuberculosis is usually accepted, the role of IL17F has been scarcely studied so far. The aim of this work was to evaluate the existence of a potential association of the non-synonymous variant rs763780 SNP of the IL17F gene with human tuberculosis. Accordingly, by comparing healthy donors (HD) and tuberculosis patients (TB) populations we demonstrated an association between the C allele of the SNP and the susceptibility to tuberculosis disease in Argentina. Furthermore, we found that peripheral blood mononuclear cells (PBMCs) from individuals with a more effective immune response against Mtb secreted the highest levels of IL17F when stimulated with a lysate of Mtb (Mtb-Ag). Besides, we evidenced that Mtb-Ag-stimulated PBMCs from HD carrying the C variant of the SNP displayed the lowest IFNG secretion, proliferation index, and SLAM expression as compared to TT carriers. Moreover, Mtb-Ag-stimulated PBMCs from TB carrying the C allele produced the lowest levels of IFNG, the highest level of IL17A, and the minimum proliferation indexes as compared to TT TB, suggesting a relationship between the C allele and tuberculosis severity. In fact, TB carrying the C allele presented a more severe disease, with the highest bacilli burden in sputum. Together, our findings identify the IL17F rs763780 SNP as a biomarker of tuberculosis susceptibility and advanced disease severity in Argentina, suggesting that IL17F could be a critical cytokine in tuberculosis immunity.
| S-EPMC6764169 | biostudies-literature
Project description:ObjectiveAbnormalities involving the TGFB1 gene and its receptors are common in several types of cancer and often related to tumor progression. We investigated the role of single nucleotide polymorphisms (SNP) in the susceptibility to cancer, their impact on its features, as well as the role of mRNA expression of these genes in thyroid malignancy.MethodsWe genotyped TGFB1, TGFBR1, and TGFBR2 SNPs in 157 papillary thyroid cancer (PTC) patients and 200 healthy controls. Further, we investigated RNA samples of 47 PTC and 80 benign nodules, searching for differential mRNA expression.ResultsSNPs rs1800472 and rs1800469 were associated with characteristics of PTC aggressiveness. Effect predictor software analysis of nonsynonymous SNP rs1800472 indicated increasing protein stability and post-translational changes. TGFB1 mRNA expression was upregulated in PTC and downregulated in benign samples, differentiating malignant from benign nodules (p<0.0001); PTC from goiter (p<0.0001); and PTC from FA (p<0.0001). TGFBR1 mRNA expression was upregulated in goiter and PTC, but downregulated in FA, distinguishing PTC from goiter (p=0.0049); PTC from FA (p<0.0001); and goiter from FA (p=0.0267). On the other hand, TGFBR2 was downregulated in all histological types analyzed and was not able to differentiate thyroid nodules.ConclusionTGFB1 polymorphism rs1800472 may confer greater activity to TGF-β1 in the tumor microenvironment, favoring PTC aggressiveness. Evaluation of TGFB1 and TGFBR1 mRNA levels may be useful to identify malignancy in thyroid nodules.
| S-EPMC10065325 | biostudies-literature
Project description:The transforming growth factor-β (TGFβ) pathway plays an important role in various types of human cancer. However, the role of TGFB1 -509C/T and TGFBR2 -875A/G polymorphisms in gastric cancer is controversial. We aimed to investigate the associations between these polymorphisms and gastric cancer susceptibility, clinicopathological parameters and survival. A case-control study was conducted in 1,010 gastric cancer patients and 1,500 healthy controls. Genotypes were determined by PCR-restriction fragment length polymorphism and DNA sequencing. Compared with the TT genotype, the TGFB1 -509 C allele (CT/CC) was significantly associated with a reduced risk of gastric cancer (OR, 0.71; 95% CI, 0.58-0.87; p=0.001) and certain subtypes of gastric cancer including intestinal type (OR, 0.70; 95% CI, 0.57-0.87; p=0.001), poorly differentiated (OR, 0.67; 95% CI, 0.54-0.85; p=0.001) and stage TNM III+IV (OR, 0.73; 95% CI, 0.58-0.92; p=0.008). Compared with the TGFBR2 -875 GG genotype, carriers of the A allele (AA/AG) had a significantly decreased gastric cancer risk (OR, 0.58; 95% CI, 0.62-0.91; P<0.001). A combination of the TGFB1 -509 C and TGFBR2 -875 A alleles was associated with a further decreased risk of gastric cancer (OR, 0.42; 95% CI, 0.32-0.57, p<0.001). No significant correlation was observed between polymorphisms and survival of gastric cancer patients. Our results suggest that both the TGFB1 -509 and TGFBR2 -875 polymorphisms contribute to a decreased gastric cancer risk. The TGFB1 -509 polymorphism affects certain subtypes of gastric cancer according to clinicopathological parameters. A combination of the TGFB1 -509 C and TGFBR2 -875 A alleles conferred a further decreased gastric cancer risk. These findings provide clues to the biological mechanisms that underline tumor heterogeneity.
| S-EPMC3410591 | biostudies-literature
Project description: Not available
| S-EPMC4380740 | biostudies-literature