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IL-17A, IL-17F and IL-23R Gene Polymorphisms in Polish Patients with Rheumatoid Arthritis.

ABSTRACT: Among the complex network of inflammatory cells involved in the pathogenesis of rheumatoid arthritis (RA), Th17 cells have recently been identified as key cells in the promotion of autoimmune processes, and joint destruction. The IL-23/Th17 signalling pathway, consisting of IL-23/IL-23R, IL-17A and IL-17F encoding genes, represents a candidate way for RA development with possible involvement in disease susceptibility and effect on disease progression. The present study aimed to determine the association between the polymorphic variants of the IL-17A (rs2275913), IL-17F (rs763780) and IL-23R (rs11209026) genes and RA susceptibility, progression and response to therapy with TNF-α inhibitors. Eighty-nine patients and 125 healthy individuals were investigated. The IL-17A polymorphism was found to affect RA progression and response to anti-TNF treatment. Female patients carrying the IL-17A wild-type genotype more frequently presented with stage 4 (8/24 vs. 6/47; p = 0.058) and were characterized by more active disease (the highest DAS28 score >5.1) after 3 months of therapy with the TNF inhibitors (12/23 vs. 15/45; p = 0.040). The IL-17F polymorphism appeared to be associated with susceptibility to the disease. The presence of the IL-17F minor variant (OR 3.97; p < 0.001) and its homozygosity (OR 29.62; p < 0.001) was more frequent among patients than healthy individuals. These results suggest that the polymorphisms within the IL-17A and IL-17F genes play a significant role in RA.

SUBMITTER: Bogunia-Kubik K

PROVIDER: S-EPMC4429134 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Correlation between acute myeloid leukemia and IL-17A, IL-17F, and IL-23R gene polymorphism.

Project description:Recent studies have shown that Th17 cells may be involved in the pathological process of acute myeloid leukemia. This CD4+ cell subgroup secretes highly homologous interleukin (IL)-17A and IL-17F, and also expresses IL-23 receptor (IL-23R) on the cell surface. Our study aims to investigate the relationship of IL-17A, IL-17F, and IL23R with disease susceptibility, and clarify the relationship between gene polymorphism variation and serum IL-17 level. 62 acute myeloid leukemia patients and 125 healthy controls were included in this study. Restriction fragment length polymorphism polymerase chain reaction (PCR-RFLP) was applied to analyze IL-17A (rs2275913; G-197A), IL17F (rs763780; A7488G; His161Arg), and IL-23R (rs11209026, G1142A; Arg381Gln) alleles. At the same time, enzyme-linked immunoassay analysis (ELISA) was used to test serum IL-17 level in patients. Acute myeloid leukemia patients presented higher rate of IL-17F G single mutant (RR=4.75, P<0.001) and GG mutation homozygote (RR=23.01, P<0.005). While IL-17A, IL-23R A single mutant and purified AA mutation homozygote showed no correlation with acute myeloid leukemia susceptibility. In addition, ELISA showed that serum IL-17 exhibited no significant difference between acute myeloid leukemia patients and healthy controls had (8.8±7.19 pg/ml vs. 1.4±0.2 pg/ml, P>0.05). IL-17F G single mutant and GG mutation homozygote were correlated with acute myeloid leukemia susceptibility, while IL-17 gene polymorphism and serum IL-17 level were not. Furthermore, IL-17A and IL-23R gene polymorphism were not associated with acute myeloid leukemia susceptibility.

| S-EPMC4503161 | biostudies-literature

<i>IL-17F</i> Gene rs763780 and <i>IL-17A</i> rs2275913 Polymorphisms in Patients with Periodontitis.

Project description:Background: Periodontitis (PD) is a chronic inflammatory disease that can eventually lead to tooth loss. Genetic and environmental factors such as smoking are involved in the pathogenesis of PD. The development of PD is potentiated by various pathogens that induce an immune response leading to the production of cytokines, such as interleukin (IL)-17. The synthesis of IL-17 is influenced genetically. The polymorphisms in IL-17 gene may affect the synthesis of IL-17. The aim of this study was to examine the association between the IL-17F rs763780 and IL-17A rs2275913 polymorphisms and PD in non-smoking and smoking patients to check if these polymorphisms could be a risk factor for PD. Methods: The study enrolled 200 patients with PD (130 non-smokers and 70 smokers) and 160 control subjects (126 non-smokers and 34 smokers). Periodontitis was diagnosed on the basis of 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions. All samples were genotyped using allelic discrimination assays with TaqMan® probes on a Real-Time PCR Detection System. Results: There were no statistically significant differences in the distribution of the IL-17F rs763780 and IL-17A rs2275913 genotypes and alleles between patients with PD and control subjects, between smoking patients with PD and smoking control subjects, and between non-smoking patients with PD and non-smoking control subjects. Conclusions: The results of this study suggest a lack of statistically significant associations between IL-17F rs763780 and IL-17A rs2275913 polymorphisms and PD in Polish population.

| S-EPMC7908462 | biostudies-literature

IL-17A, IL-17RC polymorphisms and IL17 plasma levels in Tunisian patients with rheumatoid arthritis.

Project description:Interleukin-17 (IL-17), a cytokine mainly secreted by Th17 cells, seems to play a significant role in the pathogenesis of rheumatoid arthritis (RA). Functional genetic polymorphisms in IL-17 and its receptor genes can influence either qualitatively or quantitatively their functions. Therefore, we aimed to study the impact of IL17-A and IL17RC polymorphisms on plasma level of IL-17 and RA susceptibility and severity.In this context, IL-17A*rs2275913 and IL-17RC*rs708567 polymorphisms were investigated together with the quantification of IL17 plasma level in 115 RA patients and 91 healthy control subjects matched in age, sex and ethnic origin.There were no statistically significant associations between IL-17A and IL-17RC studied polymorphisms and RA susceptibility. In contrast, IL-17A plasma levels were significantly higher in patients (55.07 pg/ml) comparatively to controls (4.75 pg/ml), p<10E-12. A ROC curve was used to evaluate the performance of plasma IL-17 in detecting RA. Given 100% specificity, the highest sensitivity of plasma IL-17A was 61.7% at a cut-off value of 18.25 pg/ml; p < 10E-21, CI = [0.849-0.939]. Analytic results showed that the IgM-rheumatoid factor and anti-CCP antibodies were significantly less frequent in patients with the IL-17RC*A/A genotype than those carrying *G/G and *G/A genotypes; p = 0.013 and p = 0.015, respectively. Otherwise, IL-17 plasma levels' analysis showed a significant association with the activity of RA (DAS28≥5.1 = 74.71 pg/ml vs. DAS28<5.1 = 11.96 pg/ml), p<10E-6.IL-17A*rs2275913 (G/A) and IL-17RC*rs708567 (G/A) polymorphisms did not seem to influence RA susceptibility in Tunisian population. This result agrees with those reported previously. Plasma IL-17A level seems to be predictive of severe RA occurrence.

| S-EPMC5870983 | biostudies-literature

IL-17A (-197G/A) and IL-17F (7488T/C) gene polymorphisms and cancer risk in Asian population: a meta-analysis.

Project description:Interleukin (IL)-17 has been shown to play an important role in the pathogenesis of inflammation and cancer. The IL-17A (-197G/A) and IL-17F (7488T/C) polymorphisms have been extensively investigated with cancer risk, but individually published results have been inconclusive. The aim of this study was to clarify the effects of the IL-17A (-197G/A) and IL-17F (7488T/C) polymorphisms on cancer risk in Asian populations. Relevant studies were identified by searching databases extensively. The association between the IL-17A (-197G/A) and IL-17F (7488T/C) polymorphisms and cancer risk was assessed by odds ratios (ORs) together with their 95% confidence intervals (CIs). A total of 12 articles with adequate information satisfied our inclusion criteria; these included 12 studies, with 4,540 cases and 5,875 controls, of IL-17A (-197G/A) polymorphism and seven studies, with 1,960 cases and 3,226 controls, of IL-17F (7488T/C) polymorphism. In the overall analysis, the IL-17A (-197G/A) polymorphism was significantly associated with increased cancer risk (P<0.05), for all genetic models. However, there was no statistically significant association between IL-17F (7488T/C) and cancer risk (P>0.05), for any genetic models. Furthermore, stratification by cancer type revealed a significant correlation between the IL-17A (-197G/A) polymorphism and cancer risk for all cancer types. When stratified by source of controls, a significant correlation was observed between the IL-17A (-197G/A) polymorphism and cancer risk in the population-based control subgroup but not in hospital-based control subgroup. In conclusion, our meta-analysis provides evidence that the IL-17A (-197G/A) polymorphism might be associated with cancer risk, while no evidence suggested a significant association between IL-17F (7488T/C) polymorphism and cancer risk.

| S-EPMC4027853 | biostudies-literature

Association analysis of IL-17A and IL-17F polymorphisms in Chinese Han women with breast cancer.

Project description:BACKGROUND: Research into the etiology of breast cancer has recently focused on the role of the immunity and inflammation. The proinflammatory cytokines IL-17A and IL-17F can mediate inflammation and cancer. To evaluate the influences of IL-17A and IL-17F gene polymorphisms on the risk of sporadic breast cancer, a case-control study was conducted in Chinese Han women. METHODOLOGY AND PRINCIPAL FINDINGS: We genotyped three single-nucleotide polymorphisms (SNPs) in IL-17A (rs2275913, rs3819025 and rs3748067) and five SNPs in IL-17F (rs7771511, rs9382084, rs12203582, rs1266828 and rs763780) to determine the haplotypes in 491 women with breast cancer and 502 healthy individuals. The genotypes were determined using the SNaPshot technique. The differences in the genotypic distribution between breast cancer patients and healthy controls were analyzed with the Chi-square test for trends. For rs2275913 in IL-17A, the frequency of the AA genotype was higher in patients than controls (P?=?0.0016). The clinical features analysis demonstrated significant associations between IL-17 SNPs and tumor protein 53 (P53), progesterone receptor (PR), human epidermal growth factor receptor 2 (Her-2) and triple-negative (ER-/PR-/Her-2-) status. In addition, the haplotype analysis indicated that the frequency of the haplotype A(rs2275913)G(rs3819025)G(rs3748067), located in the IL-17A linkage disequilibrium (LD) block, was higher in patients than in controls (P?=?0.0471 after correction for multiple testing). CONCLUSIONS AND SIGNIFICANCE: Our results suggested that SNPs in IL-17A but not IL-17F were associated with the risk of breast cancer. Both IL-17A and IL-17F gene polymorphisms may provide valuable information for predicting the prognosis of breast cancer in Chinese women.

| S-EPMC3312906 | biostudies-literature

IL-23R and IL-17A polymorphisms correlate with susceptibility of ankylosing spondylitis in a Southwest Chinese population.

Project description:The association between the IL-23R and IL-17A polymorphisms and ankylosing spondylitis (AS) in the Southwest Chinese Population is still unclear. The purpose of this study is to detect the association between IL-23R and IL-17A polymorphisms and AS. A case-control study consisting of 486 AS patients and 480 healthy controls was performed. We used the high-resolution melting methods (HRM) to genotype five selected single nucleotide polymorphisms (SNPs), rs6693831, rs7517847, rs1884444, rs10889677 in the IL-23R gene and rs2275913 in the IL-17A gene. Meanwhile, the laboratory indexes were recorded. In this study, patients with genotype CC (p = 8.574E-8) and allele C (p = 3.206E-31) on SNP rs6693831 (IL-23R) showed decreased risk of AS. The genotype TT (p = 4.551E-6) and allele T (p = 0.02) on SNP rs1884444 (IL-23R) showed significant lower risk of AS. Individuals carrying the allele A of rs2275913 showed higher morbidity of AS (p = 0.04). We first detected that rs6693831 and rs1884444 in IL-23R gene and rs2275913 in IL-17A gene have genetic association with AS.

| S-EPMC5642556 | biostudies-literature

IL-7R gene polymorphisms among patients with rheumatoid arthritis: A case-control study.

Project description:BackgroundRheumatoid arthritis (RA) is the most common inflammatory disease which refers to bony erosions and joint destruction largely caused by genetic factors. Our study aimed to explore whether interleukin-7 receptor (IL-7R) gene polymorphisms influenced RA risk in the Han Chinese population.MethodsFive single nucleotide polymorphisms (SNPs) in IL-7R gene were successfully genotyped using Agena MassARRAY platform. The associations between IL-7R polymorphisms and RA were evaluated by the Chi-squared test, T test, genetic model analysis, and haplotype analysis. We calculated odds ratios (ORs) and 95% confidence intervals (95% CIs) using logistic regression analysis.ResultsRs969129 and rs6451231 in the IL-7R gene were associated with an increased risk of RA in the allele model (OR = 1.25, 95% CI = 1.05-1.49, p = 0.013; OR = 1.23, 95% CI = 1.03-1.48, p = 0.023), respectively. In the genetic models, rs969129 and rs6451231 were associated with an increased risk of RA. After stratification analysis by age, rs969129 and rs6451231 were associated with an increased risk of RA in patients (age <54). After stratification analysis by gender, rs6451231 was associated with an increased risk of RA in males, while rs969129 was found to be associated with an elevated risk of RA in females. And there was a strong linkage disequilibrium among the four SNPs (rs969129, rs118137916, rs10053847, and rs6451231).ConclusionThese results suggested rs969129 and rs6451231 in the IL-7R gene were associated with an increased risk of RA in the Han Chinese population.

| S-EPMC6625337 | biostudies-literature

IL-17A and IL-17F producing cells

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-11-20 | GSE189232 | GEO

Frequency distribution of IL-17A G197A (rs2275913) and IL-17F A7488G (rs763780) polymorphisms among healthy Sudanese population.

Project description:OBJECTIVES:IL-17A G197A and IL-17F A7488G polymorphisms has been identified to be associated with the susceptibility to many diseases. This study aimed to investigate the frequency distribution of IL-17A G197A and IL-17F A7488G polymorphisms among healthy Sudanese population. A descriptive cross-sectional hospital-based molecular study conducted in different sites throughout Sudan. Two ml blood samples were collected from 717 healthy participants. Demographic data and the medical history of the participants were collected. RESULTS:Of the 717 participants, 355 (49.5%) were males and 362 (50.5%) were females, their mean age was 30.2?±?17.2 and 32.2?±?16.5, respectively. For IL-17A, the most frequent genotype detected among males and females was IL-17A heterozygote allele (AG); 215 (60.6%) and 194 (53.6%), respectively. Whereas, for IL-17F, the most frequent allele among males and females was the homozygote allele (AA); 298 (83.9%) for males and 322 (89.0%) for females. HWE for genotype distributions of IL-17A was showing statistical insignificance for IL-17A among males and females, P value 0.614. While HWE for IL-17F reached the equilibrium level, P value 0.048. The most frequent age group was those aged between 21 to 40 years; 281 (39.2%). Arab constituted the major ethnicity of the study participants; 418 (58.3%), P value 0.034.

| S-EPMC7330939 | biostudies-literature

Lack of Association of the Polymorphisms IL-17A (-197G/A) and IL-17F (+7488A/G) with Multibacillary Leprosy in Mexican Patients.

Project description:Background. Leprosy is a chronic infectious disease caused by the intracellular acid-fast bacilli Mycobacterium leprae; it has been determined that genetic factors of the host play an important role in the disease susceptibility. Thus, in this case-control study, we evaluated the possible association between the IL-17A G-197A (rs227593) and IL-17F A7488G (His161Arg, rs763780) gene SNPs and susceptibility to leprosy disease in Mexican population. Methods. Seventy-five leprosy patients and sixty-nine control subjects were included. Both SNPs were genotyped with the polymerase chain reaction-restriction fragment length polymorphism technique. Results. We found nonsignificant differences in genotype and allele frequencies related to IL-17A G-197A (rs227593) and IL-17F A7488G (His161Arg, rs763780) gene SNPs in MB as well as subclinical forms of leprosy disease versus healthy individuals. Conclusions. Since the sample size is not large enough, it is difficult to sustain an association of susceptibility to leprosy with genotypes or allele frequencies of IL-17A G-197A (rs227593) and IL-17F A7488G (His161Arg, rs763780), suggesting that IL-17 polymorphisms have no significant role in the genetic susceptibility to development of this disease in the Mexican Mestizo population.

| S-EPMC4241254 | biostudies-literature

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