IL-17F Rs763780 Polymorphisms Research Articles

Analysis of IL-17A, IL-17F, and miR-146a-5p Prior to Transplantation and Their Role in Kidney Transplant Recipients

Background/Objectives: The balance between regulatory and Th17 cells plays an important role in maintaining the immune tolerance after kidney transplantation (KTx) which is essential for transplantation success, defined as a long graft survival and an absence of organ rejection. The present study aimed to assess whether the pretransplant characteristics of IL-17A and IL-17F, their receptors, as well as miR-146a-5p, an miRNA associated with IL-17A/F regulation, can predict KTx outcomes. Methods: A group of 108 pre-KTx dialysis patients and 125 healthy controls were investigated for single nucleotide substitutions within genes coding for IL-17A, IL-17F, their IL-17RA/RC receptors, and miR-146a-5p. Genotyping was performed using LightSNiP assays. In addition, IL17-A/F serum concentrations were determined using ELISA while miR-146a-5p expression was analyzed by RT-PCR. Results: The IL-17F (rs763780) G allele prevailed in KTx recipients as compared to healthy individuals (OR = 23.59, p < 0.0001) and was associated with a higher IL-17F serum level (p = 0.0381) prior to transplantation. Higher miR-146a-5p expression before KTx was more frequently detected in recipients with an increased IL-17A serum concentration (p = 0.0177). Moreover, IL-17A (rs2275913) GG homozygosity was found to be associated with an increased incidence of deaths before KTx (OR = 4.17, p = 0.0307). T-cell or acute rejection episodes were more frequently observed among patients with the C allele of miR-146a-5p (rs2910164) (OR = 5.38, p = 0.0531). IL17-RA/-RC genetic variants (p < 0.05) seem to be associated with eGFR values. Conclusions: These results imply that IL-17F (rs763780) polymorphism is associated with the serum level of this cytokine and may be related to the risk of renal disease and transplant rejection together with miR-146a-5p (rs2910164), while the IL-17A (rs2275913) genotype may affect patients’ survival before KTx.

Interleukin 17F Gene Polymorphism as a Potential Protective Factor in the Immunopathology of Ocular Toxoplasmosis.

Ocular toxoplasmosis (OT) is characterised by intraocular inflammation due to Toxoplasma gondii infection. Studies have found that interleukin 17 (IL-17) plays a central role in the pathology of OT. However, nucleotide variability in IL17 and interleukin 17 receptor (IL17R) genes has not been characterised in OT. As cytokine gene polymorphisms may influence the expression of these molecules, the aim of this study was to verify whether IL17A (rs2275913), IL17F (rs763780), IL17RA (rs4819554) and IL17RC (rs708567) polymorphisms are associated with OT in a Brazilian population. This study enrolled 214 patients seropositive for T. gondii (110 with OT and 104 without) and 107 controls. Polymorphisms were identified by PCR-restriction fragment length polymorphism analysis, validated by DNA sequencing with chi-square and multivariate analyses being used to assess possible associations between polymorphisms and OT. Logistic regression under the dominant model revealed a protection factor against OT of the C mutant allele of the IL17F (rs763780) polymorphism. The T/C-C/C genotypes were significantly more common in patients without OT compared to those with OT (p value = 0.0066) and controls (p value = 0.014). Findings from this study suggest that the IL17F polymorphism may have an influence in the immunopathology of OT in Brazilian individuals.

Associations between circulating interleukin-17 levels and Behcet's disease and between IL-17 gene polymorphisms and disease susceptibility: a meta-analysis.

To systematically investigate the relationship between circulating interleukin-17 (IL-17) levels and Behçet's disease (BD) and the associations between polymorphisms in IL17 genes and BD susceptibility. We searched the Medline, Embase, and Cochrane databases for relevant articles. We performed a meta-analysis of serum/plasma IL-17 levels in BD patients and controls and evaluated the associations between IL17A rs4711998, rs8193036, and rs2275913 and IL17F rs763780 and rs2397084 polymorphisms and the risk of BD. Twelve studies, involving 901 patients with BD and 1,131 controls, were included. Our meta-analysis revealed that circulating IL-17 levels were significantly higher in the BD group than in the control group (SMD = 1.422, 95% confidence interval [CI] = 0.689-2.155, p<0.001). Subgroup analysis by data type indicated higher IL-17 levels in the BD group in both the original and calculated data populations. Stratification by publication year revealed significantly lower vitamin D levels in the SSc group in both recent and older publication years. No significant differences in IL-17 levels were observed between the active and inactive disease groups. We found no evidence of associations between BD and IL17A rs2275913, L17F rs763780, or rs2397084 polymorphisms. However, a significant association was found between BD and IL17A rs4711998 and rs8193036 polymorphisms in the pooled cohort of affected individuals compared to that in pooled controls (odds ratio [OR] = 1.347, 95% CI = 1.043-1.741, p<0.001; OR = 0.691, 95% CI = 0.542-0.880, p=0.003). This meta-analysis revealed significantly higher circulating IL-17 levels in BD patients and showed evidence of associations between IL17A rs4711998 and rs8193036 polymorphisms and BD.

Associations between interleukin 17A and 17F polymorphisms and asthma susceptibility: A meta-analysis.

Owing to their role in inflammatory reactions and immunological responses as well as their chromosomal location, interleukin (IL) 17A and 17F are regarded as candidate causal genes associated with asthma. The aim of this study was to determine whether IL17 polymorphisms are associated with susceptibility to asthma. We used the PubMed/Medline and Embase databases to search for studies reporting IL17 polymorphisms in patients with asthma and healthy controls. Meta-analyses were conducted to determine the associations between IL17A rs8193036 (-737C/T), rs2275913 (-197G/A), rs3819024 (A/G), rs3748067 (C/T), and rs4711998 (A/G) and IL17F rs763780 (7488A/G), rs2397084 (T/C), rs1889570 (C/T), rs11465553 (G/A), and rs1266828 (T/C) polymorphisms and asthma susceptibility. A total of 20 studies were included in this meta-analysis. Our results revealed the IL17A rs8193036 CC genotype was associated with asthma susceptibility (odds ratio [OR]=1.490, 95% confidence interval [CI]=1.027-2.161, p=.036). However, stratification by ethnicity indicated no association between this polymorphism and asthma in European and Asian subjects. Furthermore, no association was found between this polymorphism and asthma using the allele contrast, dominant or homozygous contrast models. No evidence of an association was found between any of the other IL17A and IL17F polymorphisms and asthma susceptibility in this meta-analysis. This meta-analysis showed that, among the studied polymorphisms, only the CC genotype of IL17A rs8193036 is associated with asthma susceptibility.

Association of Interleukin-17F Polymorphism and Mortality Predictors with the Risk of COVID-19.

Th-17 cells, a proinflammatory subset of CD4 T lymphocytes, have been suggested as a possible cause of coronavirus disease-19 (COVID-19)-related immunological injuries. The aim of this study was to investigate the relationship between IL-17F (rs763780) polymorphism and the susceptibility to and outcomes of COVID-19 infection and to determine the clinical and laboratory predictors of COVID-19 death. This case-control study included 132 COVID-19 patients and 135 healthy age- and sex-matched controls. The participants were tested for IL-17F rs763780 polymorphism via TaqMan-based genotyping and for the expression of IL-17 by enzyme-linked immunosorbent assay. This study also investigated the predictors for COVID-19 mortality. A non-statistically significant association was observed between IL-17F alleles and genotypes with COVID-19 (P=0.309, P=0.138, respectively). Moreover, no significant difference in the IL-17F genotypes was observed between non-survivors and survivors (P=0.482). In the multivariate analysis, the participants with the following characteristics had 17.7-, 11.2-, 8-, and 17.9-fold higher odds of exhibiting in-hospital mortality, respectively: (1) hypertension, (2) age of >57 years, (3) WBC count of >12.6 × 103/mm3, and (4) D-dimer of >0.9 ng/ml. The ROC curve analysis showed that IL-17 at a cutoff point of >46 pg/ml was a perfect discriminator of COVID-19 patients from control subjects (AUC = 1.0). The findings indicate that the IL-17F H161R variant does not influence the risk of COVID-19. However, the IL-17 level is a perfect discriminator of COVID-19 infection. Hypertension, age of >57 years, white blood cell count of >12.6 × 103/mm3, and D-dimer of >0.9 ng/ml are the independent predictors for death among COVID-19 patients.

IL17F rs763780 polymorphism is associated with unhealthy BMI and diabetes mellitus in patients with acute myocardial infarction

IL-17F induces expression of pro-inflammatory cytokines but its association with cardiovascular diseases is controversial. Rs763780T > C variant affects the potency of IL-17F in signaling and cytokine production. In the current study we investigated the frequency of IL-17F rs763780T > C in the patients with AMI in an Iranian population. The study group consisted of 175 AMI patients and 128 healthy blood donors. Genomic DNA was extracted from peripheral blood and genotyped by polymerase-chain-reaction restriction-fragment-length-polymorphism (PCR-RFLP). While no significant difference in the frequency of IL-17F rs763780 SNP existed between patients and controls (P = 0.82 and P = 0.72, respectively), TT genotype was associated with type-2 diabetes mellitus (P = 0.034). Patients with BMI >30 and < 25 were more likely to carry T allele (P = 0.021). TT genotype and T allele were also associated with left ventricular hypertrophy (LVH) (P = 0.001 and P = 0.032, respectively). Our data suggest that IL-17F variants are different in their relation with obesity. Obese individuals with AMI were more likely to carry the IL-17F major allele and AMI patients (but not controls) with diabetes had a higher frequency of IL-17F TT genotype, indicating the predisposing effect of T allele in inflammatory milieu. Also, the association of TT genotype and T allele with LVH may be related to the more potent induction of pro-inflammatory cytokines by IL-17F major allele. In conclusion, we suggest that IL-17F inflammatory activity affected by its SNPs could be as important as its expression level in clinical manifestations of AMI.

Associations of IL-4, IL-4R, IL-17A, and IL-17F Polymorphisms with Colorectal Cancer Risk: A Meta-Analysis, Meta-Regression, and Trial Sequential Analysis.

Both interleukin (IL)-4 and IL-17 polymorphisms may be involved in the pathogenesis and progression of colorectal cancer (CRC). Herein, we designed a meta-analysis to assess the associations between IL-4, IL-4R, IL-17A, and IL-17F polymorphisms and CRC risk. Scopus, Web of Science, Cochrane Library, and PubMed databases were searched to retrieve articles published until October 21, 2021. We used crude odds ratio (OR) and 95% confidence interval assessing the association of the polymorphisms and CRC risk in 5 genetic models. Trial sequential analysis for the primary analyses was used to control random errors. Twenty-three studies (8: IL-4 rs2243250, 4: IL-4R rs1801275, 5: IL-17A rs2275913, and 6: IL-17F rs763780) were involved in the meta-analysis. The pooled OR (P-value) for the association between IL-4 rs2243250 polymorphism and the CRC risk was 1.11 (0.08), 1.27 (0.12), 1.07 (0.37), 1.09 (0.17), and 1.22 (0.12), for IL-4R rs1801275 polymorphism was 0.71 (0.18), 1.05 (0.76), 0.86 (0.37), 0.87 (0.41), and 0.69 (0.39), for IL-17A rs2275913 polymorphism was 1.83 (0.0003), 1.73 (0.06), 1.47 (<0.001), 1.61 (0.001), and 1.42 (0.15), and for IL-17F rs763780 polymorphism was 1.07 (0.48), 5.33 (0.02), 1.08 (0.49), 1.08 (0.47), and 8.42 (0.002) in allelic, homozygous, heterozygous, recessive, and dominant models, respectively. The G allele and GA genotype of IL-17A rs2275913 polymorphism and the CC genotype of IL-17F rs763780 polymorphism had an elevated risk in CRC cases. The ethnicity and genotyping method, sample size, control, and publication year were effective factors on the pooled results.

The associations between interleukin-17 single-nucleotide polymorphism and colorectal cancer susceptibility: a systematic review and meta-analysis

BackgroundNumerous case-control studies have reported associations between interleukin-17 (IL-17) polymorphisms and colorectal cancer; however, the results were inconsistent. The aim of this meta-analysis was to further clarify the effects of IL-17 polymorphisms on colorectal cancer susceptibility.Materials and methodRelevant studies were extracted from the electronic databases PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), and the Chinese Biomedical Literature Database (CMB) up to April 2021. The odds ratio and 95% confidence interval were used to estimate the strength of the associations.ResultsTen articles including 2599 cases and 2845 controls were enrolled in our research after strict literature screening. Highly significant associations between the IL-17A rs2275913 polymorphism and increased colorectal cancer susceptibility were observed in all five gene models (allelic, dominant, recessive, homozygous, and heterozygous models), and subgroup analysis based on ethnicity revealed that these associations existed not only in the Asian population but also in the Caucasian population. However, the results showed no significantly elevated colorectal cancer risk correlated with the IL-17F rs763780 polymorphism, and a slightly lower colorectal cancer susceptibility for the Caucasian population was discovered in the recessive and homozygous models of this mutation.ConclusionThe IL-17A rs2275913 polymorphism may be an independent risk factor contributing to colorectal cancer susceptibility, while the IL-17F rs763780 polymorphism may decrease susceptibility to colorectal cancer. Future studies with large-scale samples are warranted to identify these associations.

Polymorphisms within Genes Coding for IL-17A and F and Their Receptor as Clinical Hallmarks in Ankylosing Spondylitis.

IL-17A and IL-17F together with their coreceptor (IL-17RA/RC) were reported to play a significant role in the pathogenesis of spondyloarthritis. The group of axial spondyloarthritis comprises ankylosing spondylitis (AS), a rheumatic disease characterized by chronic inflammation of the joints in the spine. This study is aimed at investigating IL-17A, IL-17F, IL-17RA, and IL-17RC polymorphisms as potential biomarkers of disease susceptibility, clinical parameters, and anti-TNF treatment outcome in a cohort of Polish ankylosing spondylitis patients. In total, 328 subjects, including 138 AS patients and 190 healthy volunteers, participated in the study. Genotyping of IL-17A rs2275913 (G/A), IL-17F rs763780 (A/G), IL-17RA rs4819554 (A/G), and IL-17RC rs708567 (G/A) was performed on real-time PCR instrument using LightSNiP assays. No significant differences were revealed in genotype and allele distribution between patients and controls despite the association of the IL-17RC rs708567 AA homozygosity with the earlier onset of the disease. Moreover, some relationships between IL-17F rs763780 and IL-17RA rs4819554 polymorphisms with clinical parameters related to the disease activity and anti-TNF treatment outcome were observed. IL-17F rs763780 G allele was found to be associated with high disease activity and BASDAI after 6 months and poor response to the treatment while higher VAS values were more common among IL-17RA rs4819554 G variant carriers. In conclusion, the IL-17F rs763780 polymorphism should be considered as a promising biomarker of disease activity and anti-TNF treatment outcome. The IL-17RA rs48419554 G allele may serve as a potential marker of disease severity in Polish AS patients.

Association between IL-17A, IL-17F and IL-17RA gene polymorphisms and susceptibility to psoriasis and psoriatic arthritis: a meta-analysis.

Psoriasis (Ps) is a chronic dermatosis characterized by erythematous-squamous plaques derived from an inflammatory response. The effect of polymorphisms in the genes that encode the members of the IL-17 family and their receptors has been studied to find an association with the susceptibility to Ps. However, the findings have not been conclusive. To describe the association between IL-17A, IL-17F and IL-17RA gene polymorphisms and susceptibility to Ps. A systematic review was conducted using the PubMed and Scopus databases to identify studies that evaluated the association between IL-17A, IL-17F, and IL-17RA gene polymorphisms and Ps susceptibility. This meta-analysis included reports published until June 2021. Heterogeneity was assessed using Cochran's Q-statistic test and I2 statistics. The associations between polymorphisms and Ps susceptibility were determined by pooled OR with a 95% CI. Fifteen studies were included. The frequency of the T allele of the IL-17F rs763780 polymorphism was significantly lower in patients with vulgar Ps (OR = 0.732, p = 0.026). The TT genotype of the IL-17F rs763780 polymorphism was significantly associated with a decreased frequency in individuals with Ps and psoriatic arthritis (PsA) (TT:TC + CC OR = 0.664, p = 0.046). Regarding IL-17RA polymorphisms, the AG genotype of the rs4819554 polymorphism showed a near-significant decrease in psoriasis risk compared to the GG genotype (AG:GG OR = 0.604, p = 0.050). Other polymorphisms in IL-17A, IL-17F and IL-17RA showed no association with Ps. The T allele and TT genotype of the IL-17F rs763780 polymorphism may be associated with a decreased risk of psoriasis. Therefore, the implications of this variant on psoriasis pathogenesis and treatment require further investigation.

Influence of IL10 (rs1800896) Polymorphism and TNF-α, IL-10, IL-17A, and IL-17F Serum Levels in Ankylosing Spondylitis.

Ankylosing spondylitis (AS) is a chronic autoimmune inflammatory disease that mainly affects the axial and sacroiliac joints. Single-nucleotide polymorphisms (SNPs) in genes encoding cytokines have been associated with AS, which can interfere with the production of these cytokines and contribute to the development of AS. In order to contribute to a better understanding of the pathology of AS, our objective was to investigate a possible association of the IL10 −1082 A>G SNP (rs1800896) with AS and to evaluate the serum levels of TNF-α, IL-10, IL-17A, and IL-17F in AS patients and controls comparing them with their respective genotypes (TNF rs1800629, IL10 rs1800896, IL17A rs2275913, and IL17F rs763780). Patients and controls were selected from the Maringá University Hospital and the Maringá Rheumatism Clinic, in Paraná State, Southern Brazil, and they were diagnosed by the ASAS Criteria. In total, 149 patients and 169 controls were genotyped for the IL10 −1082 A>G polymorphism using a polymerase chain reaction with sequence specific primers (PCR-SSP); the measurement of TNF-α serum levels was performed through the immunofluorimetric test and IL-10, IL-17A, and IL-17F using an ELISA test. There was a high frequency of the IL10 −1082 G allele in AS patients compared with controls with an odds ratio of 1.83 and 95% confidence interval of 1.32 to 2.54, and a significant difference in the genotype frequencies of the IL10 −1082 A/G+G/G between patients and healthy controls, with an odds ratio of 3.01 and 95% confidence interval of 1.75 to 5.17. In addition, increased serum levels of IL-10 were observed in AS patients: 2.38 (IQR, 0.91) pg/ml compared with controls 1.72 (IQR 0.93) pg/ml (P = 0.01). Our results also showed an association between IL17F rs763780 C/T+T/T genotypes and increased serum levels of IL-17F in patients with AS and also in controls. We can conclude that patients with the A/G and G/G genotypes for −1082 A>G (rs1800896) in the IL10 gene are three times more likely to develop AS, that the serum level of IL-10 was higher in AS patients and that the IL17F rs763780 polymorphism can affect the levels of IL-17F in the serum of patients and controls in the same way.

IL-17 Genetic Variations Increase The Risk of Cirrhotic/Hepatocellular Carcinoma in Patients with Hepatitis B Virus Infection.

Genetic variation in immune regulatory genes might influence the HBV infection outcome. This study aimed to determine the association of IL-17A rs2275913 (G197A), IL-17F rs763780 (A7488G), and IL-23R rs10889677 (C2370A) gene polymorphisms, as well as the emerged haplotypes in the individual infected by HBV and to investigate their association with the infection outcome. 300 chronic HBV infections with Cirrhotic/Hepatocellular carcinoma(C/HCC), chronic active (CA), and asymptomatic carrier (AC) and 38 individuals whose infection was spontaneously cleared (SC) were enrolled. Genomic DNA was extracted, and IL-17A/F and IL-23R genotyping were performed by using the PCR-RFLP method. Out of 338 subjects, 238 and 100 were respectively male and /female with a mean age of 47.61±13.41. The frequency of GA genotype (p=0.01) and A alleles (p=0.001) of IL-17A rs2275913 (G197A), as well as the frequency of AA genotype (p=0.014) and A alleles (p=0.018) of IL-17F rs763780 (A7488G) gene locus, was found to be significantly higher in the C/HCC than CA and AC groups. Furthermore, the frequency of GA and AG haplotype in CA individuals was higher than those with C/HCC and AC (p=0.003). Also, the GG haplotype was higher in AC individuals than those with C/HCC (P=0.022), and the AA haplotype was higher in C/HCC individuals than the CA patients (P=0.001). Our findings suggest that A allele and GA genotype at IL-17A rs2275913 (G197A), as well as A allele and AA genotype at IL-17F rs763780 (A7488G) locus, might be associated with increased risk of C/HCC among patients with hepatitis B virus infection.

IL-17F Gene rs763780 and IL-17A rs2275913 Polymorphisms in Patients with Periodontitis

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.

Il17A (rs2275913 G&gt;A) and IL17F (rs2397084 T&gt;C) gene polymorphisms: relation to psoriasis risk and response to methotrexate

Background IL17F rs763780 polymorphism results in substitution of histidine to arginine at amino acid 161, leading to upregulation of IL17F and increased propensity to autoimmune diseases. The single nucleotide polymorphism rs2275913 (G197A) involves a substitution of the guanine by an adenine nucleotide base in IL17A gene promotor which plays a key role in regulation of cytokine transcription. The relation of IL17 polymorphisms however to psoriasis risk and response to methotrexate has not been previously studied in Egyptians. Objective To study the relation of IL17A (rs2275913 G>A) and IL17F (rs2397084 T>C) polymorphisms to psoriasis risk and assess their predictive role regarding response to methotrexate. Patients and methods The study was conducted in two phases. First, a case–control study including 100 patients with chronic plaque psoriasis and 100 healthy control patients was conducted for IL17A (rs2275913) and IL17F (rs2397084) polymorphisms by real-time PCR. Second, a cohort study was adopted where the patients with psoriasis were treated with methotrexate weekly intramuscularly (0.6 mg/kg) for 12 weeks and followed for clinical response. Results IL17F TT genotype was more frequent in patients (87%) than controls (68%), whereas TC genotype was more frequent in controls (32%) than patients (13%). TT genotype was associated with increased risk of psoriasis, whereas the TC allele was associated with a decreased risk. There was no significant difference regarding IL17A GG, GA, and AA genotype frequencies between patients and controls. Psoriasis area and severity index greater than or equal to 75% was achieved in 22 patients (73.3%) with the TT genotype and eight patients (26.7%) with TC genotype (P=0.019). Conclusion IL17F (rs2397084 T>C) TT genotype could be considered a susceptibility marker in Egyptian patients. Psoriatic patients with TT genotype and T allele of IL17F (rs2397084 T>C) are likely to show a better response to methotrexate.

Association of IL-17 and IL-23 Gene Variants with Plasma Levels and Risk of Vulvovaginal Candidiasis in a Chinese Han Population.

BackgroundVulvovaginal candidiasis (VVC) is a common vaginal inflammatory disease in females. The interleukin (IL)-23/IL-17 axis was involved in vaginal inflammation. Nevertheless, the relationship between gene polymorphisms in the IL-23/IL-17 axis and VVC risk is still unexplored.MethodsWe enrolled 217 VCC cases and 326 controls in this study. The genotyping of all polymorphisms was implemented by PCR-RFLP methods.ResultsData indicated that IL-17F gene rs763780, IL-17A gene rs2275913, and IL-23R rs11209026 polymorphisms were linked with an elevated risk of VVC in Chinese ethnicity. Subgroup analyses uncovered that IL-23R rs11209026, IL-17A rs10484879 and IL-17F rs763780 polymorphisms increased the risk of VVC among smokers or individuals with BMI ≥25 kg/m2. Additionally, IL-17F rs763780 polymorphism was shown to increase the risk of recurrent VVC (RVVC). Furthermore, IL-23 and IL-17 serum levels were higher among VVC cases than controls. We also observed that IL-23 and IL-17 gene polymorphisms were related to their serum levels. Receiver operating characteristics (ROC) curve analysis found that IL-17 and IL-23 serum levels were associated with the relapse of VVC.ConclusionIn conclusion, this study indicates that polymorphisms in the IL-23/IL-17 axis increase the risk of VVC.

Interleukin 17F gene variations showed no association with BCG osteitis risk after newborn vaccination

Interleukin-17 (IL-17) family cytokines promote the host defence against mycobacterial infections. We have previously shown an association between IL17A variations and Bacillus Calmette-Guérin(BCG) osteitis. This paper evaluates the association of three IL17F polymorphisms with BCG osteitis after newborn vaccination. IL17F rs763780, rs11465553 and rs7741835 single nucleotide polymorphisms (SNPs) were studied in 132 adults, who presented with BCG osteitis in infancy. The genotypes and minor allele frequencies (MAFs) were compared between cases and Finnish population-based controls (N=99) from the 1000 Genomes Project, and MAFs were compared between cases and allele data of Finnish subjects from the large Genome Aggregation Database. There were no significant differences between former BCG osteitis patients and population-based controls in the IL17F rs763780 (wild 84.4% vs 84.8%), rs11465553 (86.4% vs 91.9%) or rs7741835 (65.7% vs 67.7%) genotypes. Homozygous variant genotypes were only present in 1.5%, 0.8% and 3.8% of cases, respectively. Likewise, MAFs of the three IL17F SNPs did not substantially differ from those of 11252, 11939 and 1371 Finnish subjects, respectively, from the available Genome Aggregation Database. IL17F rs763780, rs11465553 and rs7741835 variations showed no association with the risk of BCG osteitis after newborn vaccination.

IL17F rs763780 single nucleotide polymorphism is associated with asthma after bronchiolitis in infancy.

Interleukin-17F (IL-17F) is involved with asthma. The aim of this study was to evaluate the association of IL17F polymorphisms with childhood asthma after bronchiolitis in infancy. We invited 166 children who were hospitalised for bronchiolitis at younger than 6months of age to follow-up visits at 5-7years and 11-13years of ages. Asthma and allergy diagnoses, asthma-presumptive symptoms and use of inhaled corticosteroids (ICSs) were registered. Blood samples were available for IL17F rs763780 (T/C), rs11465553 (C/T) and rs7741835 (C/T) determinations in 165 cases. The presence of IL17F rs11465553 and rs7741835 variations showed no significant associations with any asthma or allergy outcome at either 5-7years or 11-13years of ages. Instead, children with the variant IL17F rs763780 genotype had used more often ICSs between the follow-up visits from 5-7 to 11-13years (adjusted OR 3.58) than those with the wild genotype. Children with the variant IL17F rs763780 genotype reported more often doctor-diagnosed atopic dermatitis (adjusted OR 2.71) at 11-13years of age than those with the wild genotype. This prospective long-term follow-up study provided preliminary evidence on the association of the IL17F rs763780 polymorphism with asthma at school age after bronchiolitis in infancy.

Potential effects of IL-17A rs2275913 and IL-17F rs763780 polymorphisms on susceptibility to gastric cancer in Chinese population: a meta-analysis.

This meta-analysis aims to clarify the effect of IL-17 polymorphisms on the susceptibility to GCa in the Chinese population. Relevant pieces of literature were searched in PubMed, Web of School, VIP, and CNKI using the key words as "IL-17, gastric/stomach cancer" or "IL-17 polymorphisms, gastric/stomach cancer susceptibility". The odds ratio (OR) and 95% confidence interval (CI) in the selected studies were calculated using RevMan5.3 and STATA12.0. A total of 12 investigations reporting mutations in IL-17A rs2275913 and IL-17F rs763780 were enrolled. There were 11 studies reporting rs2275913 G>A, involving 3299 cases of GCa patients and 3339 cases of healthy controls. The random-effects model was performed since the heterogeneity test results of the recessive genetic model (GG&GA vs. AA) and the allelic model (G vs. A) of IL-17A rs2275913 G>A were I2>66%/p=0.001. Meanwhile, the dominant genetic model (GG vs. GA&AA) and the super-dominant genetic model (GA vs. GG&AA) of IL-17A rs2275913 G>A were I2< 50%/p>0.05, and the fixed-effects model was used. The meta-analysis showed that IL-17A rs2275913 G>A was positively correlated with GCa susceptibility under four genetic models (p<0.05). Five studies reporting IL-17F rs763780 T>C were enrolled, including 2535 cases of GCa patients and 2402 cases of healthy controls. The heterogeneity test showed that, except for the super-dominant genetic model, the p-value was <0.00001 in the dominant, recessive, and allelic models, and their I2 values were 87%, 88%, and 93%, respectively. Hence, a random-effects model was selected. IL-17F rs763780 T>C was positively correlated with GCa susceptibility under the super-dominant genetic model (p=0.003), rather than the other three models (p>0.05). IL-17A rs2275913 G>A polymorphism contributes to susceptibility to GCa in the dominant, recessive, allelic, and super-dominant models. Meanwhile, IL-17F rs763780 T>C polymorphism is positively correlated with GCa susceptibility in the super-dominant model.

Associations Between Circulating Interleukin-17 Levels and Systemic Lupus Erythematosus and Between Interleukin-17 Gene Polymorphisms and Disease Susceptibility: A Meta-analysis

Objective. To systematically investigate the relationship between circulating interleukin-17 (IL-17) levels and systemic lupus erythematosus (SLE) and associations between polymorphisms in IL17 genes and SLE susceptibility. Methods. We performed a meta-analysis of serum/plasma IL-17 levels in patients with SLE and controls and evaluated the associations between the IL17A rs2275913, IL17F rs763780, and IL17F rs2397084 polymorphisms and IL17F copy number variations (CNVs) and risk of SLE. Results. Thirteen studies focusing on 2,096 patients with SLE and 2,587 controls were included. Our meta-analysis revealed that IL-17 levels were significantly higher in the SLE group than the control group (standardized mean difference=1.045, 95% confidence interval [95% CI]=0.521∼1.568, p＜0.001). Subgroup analysis using sample size showed increased IL-17 levels in samples from large (n＞100) but not small (n＜90) SLE groups. We found no evidence of associations between SLE and the IL17A rs2275913, IL17F rs763780, and IL17F rs2397084 polymorphisms. However, a significant association was found between SLE and IL17F CNVs in a pooled cohort of affected individuals compared to that in pooled controls (odd ratio=3.663, 95% CI=2.466∼5.221, p＜0.001). Conclusion. This meta-analysis revealed significantly higher circulating IL-17 levels in patients with SLE and showed evidence of associations between IL17F CNVs and SLE. (J Rheum Dis 2020;27:37-44)

Association between the polymorphism of IL-17A and IL-17F gene with knee osteoarthritis risk: a meta-analysis based on case-control studies

BackgroundKnee osteoarthritis is a joint disease which is characterized by degeneration of articular cartilage and subsequent subchondral bone changes. Polymorphisms of IL-17A/F gene were the recognized candidate genes associated with knee osteoarthritis risk although the results were conflicting. The aim of this study was to determine whether IL-17A(rs2275913) and IL-17F(rs763780) polymorphisms confer susceptibility to knee osteoarthritis.MethodLiterature search was performed in PubMed, Medline, Cochrane Library, Web of science, Embase, and Google Scholar (last search was updated on June 20, 2019), and assessing this association was performed by calculating odds ratios with 95% confidence intervals. Statistical heterogeneity was quantitatively evaluated by using the Q statistic with its p value and I2 statistic.ResultSix case-control based studies were included involving IL-17A(rs2275913) (2134 cases and 2306 controls) and IL-17F(rs763780) (2134 cases and 2426 controls). The overall analysis suggested that the A allele of the rs2275913 polymorphism, and the C allele of the rs763780 polymorphism in the IL-17 gene may increase the risk of OA. However, subgroup analysis revealed that no association between IL-17A(rs2275913) gene and knee OA risk was found in Caucasian population.ConclusionsThis meta-analysis revealed that the IL-17A(rs2275913) gene polymorphisms may increase the risk of knee OA in Asians, and the IL-17F(rs763780) gene polymorphisms may increase the risk of knee OA both in Asians and Caucasians. However, because of the limitations of the present study, additional larger studies are needed to confirm our findings in the future.