IL-17A Rs2275913 Research Articles

Intervertebral disc degenerative disease in South Africa: a case-control analysis of selected gene variants

BackgroundIntervertebral disc (IVD) degenerative disease is a multifactorial disease for which genetics plays an integral role. Several genes, and their variants, associated with the development and progression of IVD degenerative disease have been identified. While several studies have investigated these genes in Asian and European populations, no available evidence exists for the South African population. Therefore, this study aimed to investigate these parameters.Methods and resultsBiological samples were collected in the form of buccal swabs from patients and DNA was extracted using a standard salt-lysis protocol. DNA purity and quantity was assessed by spectrophotometry, and subsequent genotyping was performed using the MassARRAY®System IPLEX extension reaction. For associations between variants and the presence of IVD degenerative disease, odds ratios (OR), confidence intervals (CI), chi-squared analysis and logistic regression was calculated. Age and sex were adjusted for, and Bonferroni’s correction was applied. This study found statistically significant associations for five of the evaluated single nucleotide polymorphisms (SNPs) with IVD degenerative disease, whereby IL-1α rs1304037 and rs1800587, ADAMTs-5 rs162509, and MMP-3 rs632478 demonstrated increased odds of a positive diagnosis for IVD degenerative disease, while decreased odds of IVD degenerative disease were seen for GDF-5 rs143383.ConclusionTo the best of our knowledge, this study represents the first of its kind to investigate the association of gene variants associated with IVD degenerative disease within the South African population. This study has shown that 5 of these gene variants were significantly associated with the presence of IVD degenerative disease, reflecting their integral roles in development and possible progression of the disease.

Interleukin 6 and interleukin 17A serum levels and gene- polymorphisms in the development of early allograft rejection in living donor liver transplant recipients

The aim of this study is to evaluate the role of serum level of Interleukin 6(IL-6) and Interleukin 17 (IL-17) in liver transplantation outcome for living recipients, Analyze the relation between the gene polymorphism and the occurrence of rejection after liver transplantation and Study the relation between the gene polymorphism and the occurrence of different infectious complications. The study was conducted in March 2023 and included 60 healthy volunteers from the National Liver Institute (NLI) blood bank at Menoufia University and 120 live donation liver recipient patients at NLI. During one month of liver transplantation, the cytokine levels (IL-17, IL-6 proteins, IL-6 G-174C, and IL-17 A rs2275913 gene polymorphism) and CD4 levels for 60 patients of 120 live donation liver recipient patients whom early reject transplanted tissue and the same parameters were measured after 6 months follow up for non-reject group. The main finding of this study was that the post-transplant rejection group and the post-transplant non-rejection and control groups differed significantly in the genotype frequency (CC, CG, and GG) or alleles of IL-6 G-174C (p = 0.011). On the other hand IL-17A rs2275913 gene polymorphism and its alleles (p = 0.71) showed no statistically significant difference. We also observed that serum IL-17 levels, with 100% specificity and 100% sensitivity threshold, will be more sensitive and specific than serum IL-6 and CD4 count in differentiating post-transplant rejection from non-rejection patients. The results showed that there was no significant relationship between the genotypes and serum levels of interleukins and the type and degree of rejection. Proinflammatory cytokines might be useful indicators for distinguishing and early identifying unfavorable outcomes after transplantation, allowing for prompt and effective treatment intervention. To evaluate these findings, prospective clinical trials are required.

Association of IL-17A and IL-10 Polymorphisms with Juvenile Idiopathic Arthritis in Finnish Children.

To analyze the role of interleukin IL-17A and IL-10 polymorphisms in susceptibility to juvenile idiopathic arthritis (JIA), 98 Finnish children and adolescents with JIA were studied. Data from the 1000 Genomes Project, consisting of 99 healthy Finns, served as the controls. The patients were analyzed for four IL-17A and three IL-10 gene-promoter polymorphisms, and the serum IL-17A, IL-17F, IL-10, and IL-6 levels were determined. The IL-17A rs8193036 variant genotypes (CT/CC) were more common among the patients than controls, especially in those with polyarthritis (OR 1.93, 95% CI 1.11-3.36; p = 0.020). IL-17A rs2275913 minor allele A was more common in patients (OR 1.45, 95% Cl 1.08-1.94; p = 0.014) and especially among patients with oligoarthritis and polyarthritis than the controls (OR 1.61, 95%CI 1.06-2.43; p = 0.024). Carriers of the IL-17A rs4711998 variant genotype (AG/AA) had higher serum IL-17A levels than those with genotype GG. However, carriers of the variant genotypes of IL-17A rs9395767 and rs4711998 appeared to have higher IL-17F levels than those carrying wildtype. IL-10 rs1800896 variant genotypes (TC/CC) were more abundant in patients than in the controls (OR 1.97, 95%CI 1.06-3.70; p = 0.042). Carriers of the IL-10 rs1800896 variant genotypes had lower serum levels of IL-17F than those with wildtype. These data provide preliminary evidence of the roles of IL-17 and IL-10 in the pathogenesis of JIA and its subtypes in the Finnish population. However, the results should be interpreted with caution, as the number of subjects included in this study was limited.

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.

Association of Interleukin-17A and Interleukin-17F Gene Polymorphisms with Atopic Dermatitis in Chinese Children.

Background: Atopic dermatitis (AD) is a chronic, recurrent inflammatory disease associated with an unbalanced immune response in the upper layers of the skin tissue, mostly starting in childhood. As important factors in gene expression regulation, polymorphisms in interleukin (IL)-17A and IL-17F may be associated with the susceptibility and severity of AD. Methods: Blood samples and clinical information were obtained from 132 patients with AD and 100 healthy children. Using multiplex polymerase chain reaction and next-generation sequencing, five potential single-nucleotide polymorphisms (SNPs) of IL-17A and IL-17F were genotyped in all participants. The relationship between SNPs and susceptibility to or severity of AD was examined by analyzing haplotypes and genetic models. Results: The IL-17A rs3819025 polymorphism was substantially associated with higher AD risk in both the allele model (p = 0.03; odds ratio [OR] = 1.76; confidence interval [CI]: 1.05-2.95) and the dominant model (p = 0.04, OR = 1.85; CI: 1.03-3.33). There was no correlation between AD susceptibility and the IL-17A (rs2275913 and rs4711998) or IL-17F (rs763780 and rs12203736) SNPs (all p > 0.05). Additionally, the five IL-17A and IL-17F SNPs did not significantly differ across the mild-to-moderate and severe subgroups (all p > 0.05). Conclusions: The IL-17A/rs3819025 polymorphism was linked to the development of AD, whereas the IL-17F polymorphism was unrelated to the susceptibility to and severity of AD. The IL-17A polymorphism may provide valuable information to speculate on the susceptibility to AD in Chinese Han children.

Association of the IL1A and IL6 polymorphisms with posttraining changes in body mass, composition, and biochemical parameters in Caucasian women.

Polymorphisms located in IL1A and IL6 are promising markers of obesity-related traits; however, studies concerning their potential impact on the effectiveness of lifestyle interventions are lacking. Therefore, the aim was to examine the association between the polymorphic sites located in IL1A (rs1800587) and IL6 (rs1800795, rs1800796, and rs1800797) and the body's response to a 12-week training program. We studied the genotype distribution in a group of 168 Caucasian females in whom body mass and composition parameters, the lipid profile, and glucose levels were measured before and after the exercise period. Our results showed that carriers of the IL1A rs1800597 CC genotype exhibited a significant decrease in total body water (TBW) in response to training (p = 0.045). Additionally, carriers of the IL6 rs1800797 GG and GA genotypes demonstrated a posttraining decrease in body mass index (BMI) (p = 0.039). Haplotype analysis revealed that only rare haplotypes, namely, GGA, CGG and CCG (rs1800795, rs1800796, and rs1800797, respectively), were linked to changes in phenotype, yet assessing individual haplotype effects was not possible. Studies of the interactions between these genes showed that carrying the TC-GG genotype (rs1800587-rs1800795 and rs1800587-rs1800796) may be associated with greater posttraining decreases in fat mass percentage (%FM) and fat-free mass (FM). Carriers of the CC-CG genotype (rs1800587-rs1800795) had significantly greater changes in triglycerides (TGL) over the training period. Our study showed that the IL1A and IL6 genotypes, either individually, in haplotype, or in gene-gene combination, may modify training-induced changes in body mass, composition, glucose levels, and the lipid profile in healthy women.

Association between single nucleotide polymorphisms of interleukin-35 genes and atopic dermatitis.

The pathogenesis of atopic dermatitis (AD) involves complex interactions between environmental factors, the skin microbiome, epidermal barrier defects, and altered immune responses that develop on a not fully understood specific genetic background. We aimed to evaluate the contribution of single nucleotide polymorphisms (SNPs) in the IL-35 genes (IL-12A and EBI3) towards AD susceptibility and clinical characteristics of AD in the Polish population. Two SNPs (rs568408, rs582054) in IL-12A and one SNP (rs428253) in EBI3 were selected. Blood samples were collected from 202 AD patients and 178 healthy individuals. SNPs in IL-35 genes were analysed by the polymerase chain reaction with sequence-specific primers (SSP-PCR) method. For IL-12A rs568408, the AA genotype was significantly linked to increased odds of AD (OR = 34.61; 95% CI: 2.06-579.97, p = 0.0137) and marginally associated with normal total serum IgE levels (OR = 2.82; 95% CI: 0.97-8.16; p = 0.05), while the GA genotype showed significantly reduced odds of AD (OR = 0.53; 95% CI: 0.34-0.81; p = 0.0035). In the context of IL-12A rs582054, TT genotype carriers had increased odds of AD (OR = 2.05; 95% CI: 1.08-3.85; p = 0.03). Patients with the GG genotype of EBI3 rs428253 had decreased odds of high total serum IgE levels (OR = 0.42; 95% CI: 0.20-0.86; p = 0.02) and milder pruritus severity compared to CC genotype carriers (4.12 vs. 7.50; p = 0.02). IL-35 genetic variations appear to play a role in AD pathogenesis.

Association of Polymorphisms of the IL-17A and IL-17F Genes with Increased Risk of Hypertension and Obesity in Mexican Patients with COVID-19.

Coronavirus disease 2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV2). COVID-19 can cause a cytokine release syndrome in which cytokines, including interleukin 17 (IL-17), are massively secreted in response to a specific stimulus. This can contribute to mortality and severe forms of COVID-19. The study aimed to determine the association of SARS-CoV2 infection with the IL-17A rs2275913 and IL-17F rs763780 variants, as well as with the associated comorbidities in COVID-19-positive Mexican patients. The study included 178 patients positive to COVID-19 and 177 COVID-19 negative subjects. For genotyping, the samples were amplified with a TaqMan® probe. There was no association between the AA genotype and A allele of IL-17A variant or the IL-17F C allele with the presence of COVID-19. In regard to comorbidities, a statistically significant association was found between IL-17A rs2275913 AA genotype and hypertension, as well as with the presence of obesity (P = 0.003, OR 23, 95% CI: 2.97-178.092 and P = 0.025, OR 28, 95% CI: 1.52-178.029, respectively) in patients with COVID-19. In conclusion, rs2275913 IL-17A polymorphism in COVID-19 patients seems to confer a higher susceptibility to the presence of hypertension and obesity, increasing the risk of premature cardiovascular disease in this population. However, more studies should be conducted for a better understanding of their relation.

The role of IL10 and IL17 gene polymorphisms in treatment response in children and adolescents with severe asthma.

To determine whether polymorphisms of the IL10 and IL17 genes are associated with severe asthma control and bronchodilator reversibility in children and adolescents with severe asthma. This was a cross-sectional study, nested within a prospective cohort study of patients with severe asthma. Two outcomes were evaluated: asthma control and bronchodilator reversibility. We extracted DNA from peripheral blood and genotyped three single nucleotide polymorphisms: rs3819024 and rs2275913 in the IL17A gene; and rs3024498 in the IL10 gene. For the association analyses, we performed logistic regression in three genetic models (allelic, additive, and dominant). The rs3024498 C allele in the IL10 gene was associated with failure to achieve asthma control despite regular treatment (p = 0.02). However, the G allele of the IL17A rs3819024 polymorphism was associated with failure to respond to stimulation with a b2 agonist. The rs2275913 polymorphism of the IL17A gene showed no relationship with asthma control or bronchodilator reversibility. In pediatric patients with severe asthma, the IL10 polymorphism appears to be associated with failure to achieve clinical control, whereas the IL17A polymorphism appears to be associated with a worse bronchodilator response. Knowledge of the involvement of these polymorphisms opens future directions for pharmacogenetic studies and for the implementation of individualized therapeutic management of severe asthma in pediatric patients.

Impact of IL-6 rs1800795 and IL-17A rs2275913 gene polymorphisms on the COVID-19 prognosis and susceptibility in a sample of Iranian patients

BackgroundFrom asymptomatic to acute and life-threatening pulmonary infection, the clinical manifestations of COVID-19 are highly variable. Interleukin (IL)-6 and IL-17A are key drivers of hyper inflammation status in COVID-19, and their elevated levels are hallmarks of the infection progression. To explore whether prognosis and susceptibility to COVID-19 are linked to IL-6 rs1800795 and IL-17A rs2275913, these single-nucleotide polymorphisms (SNPs) were assessed in a sample of Iranian COVID-19 patients. MethodsThis study enrolled two hundred and eighty COVID-19 patients (140 non-severe and 140 severe). Genotyping for IL-6 rs1800795 and IL-17A rs2275913 was performed using tetra primer-amplification refractory mutation system-polymerase chain reaction (tetra-ARMS-PCR). IL-6 and IL-17A circulating levels were measured using enzyme-linked immunosorbent assay (ELISA). Also, mortality predictors of COVID-19 were investigated. ResultsThe rs1800795 GG genotype (78/140 (55.7 %)) and G allele (205/280 (73.2 %)) were significantly associated with a positive risk of COVID-19 severe infection (OR = 2.19, 95 %CI: 1.35–3.54, P =.006 and OR = 1.79, 95 %CI: 1.25–2.56, P <.001, respectively). Also, rs1800795 GG genotype was significantly linked to disease mortality (OR = 1.95, 95 %CI: 1.06–3.61, P =.04). The rs2275913 GA genotype was protective against severe COVID-19 (OR = 0.5, 95 %CI: 0.31––0.80, P =.012). However, the present study did not reveal any significant link between rs2275913 genotypes with disease mortality. INR ≥ 1.2 (OR = 2.19, 95 %CI: 1.61–3.78, P =.007), D-dimer ≥ 565.5 ng/mL (OR = 3.12, 95 %CI: 1.27–5.68, P =.019), respiratory rate ≥ 29 (OR = 1.19, 95 %CI: 1.12–1.28, P =.001), IL-6 serum concentration ≥ 28.5 pg/mL (OR = 1.97, 95 %CI: 1.942–2.06, P =.013), and IL-6 rs1800795 GG genotype (OR = 1.95, 95 %CI: 1.06–3.61, P =.04) were predictive of COVID-19 mortality. ConclusionThe rs1800795 GG genotype and G allele were associated with disease severity, and INR, D-dimer, respiratory rate, IL-6 serum concentration, and IL-6 rs1800795 GG genotype were predictive of COVID-19 mortality.

The association of IL-17A rs2275913 single nucleotide polymorphism with anti-tuberculous drug resistance in patients with pulmonary tuberculosis

BackgroundDrug-resistant Tuberculosis (DR-TB) is a global health burden with high morbidity and mortality in developing countries including Egypt. The susceptibility to infection with DR-TB strains may be genetically determined. Several interleukin gene polymorphisms were investigated as risk factors for tuberculosis infection but focusing on their association with DR-TB was limited. Therefore, the objective of this study is to assess the association of IL 17 − 197 G > A (rs2275913) single nucleotide polymorphism (SNP) with susceptibility to DR-TB strains in comparison to drug-sensitive tuberculosis (DS-TB) strains in Egyptian patients with pulmonary TB. This cross-sectional study was conducted on 80 patients with DR-TB strains and 80 with DS-TB strains as a control group. Both age and sex were comparable among the study’s groups. IL-17 − 197 G > A (rs2275913) SNP was genotyped by real-time PCR, and IL-17 serum concentration was measured by enzyme-linked immunosorbent assay (ELISA). ResultsThe GA and AA genotype frequencies of IL 17 − 197 G > A (rs2275913) SNP were significantly higher in patients with DR-TB strains than those with DS-TB strains (p < 0.001). The frequency of the A allele was significantly (p < 0.001) higher in patients with DR-TB group (32.5%) compared to the control group (13.8%). Substantial higher serum levels of IL-17 were detected in the DR-TB group with significant association with AA and AG genotypes. ConclusionPolymorphism in IL-17 -197 G > A (rs2275913) resulted in higher serum levels of IL-17 and Egyptian patients with such polymorphism are three times at risk of infection with DR-TB strains than patients with wild type.

Analysis of polymorphic loci of candidate genes in patients with occupational diseases

Introduction. Development and progress features of vibration syndrome (VS) and noise-induced hearing loss (NIHL) are determined by genetic factors to a certain extent. The latter define the relevance of the search for individual approaches to prevention and medical support of patients with these occupational diseases.&#x0D; The aim of the study was to investigate the genotypes distribution of polymorphic loci of candidate genes in patients with occupational diseases caused by vibration and noise impact.&#x0D; Materials and methods. Polymorphic variants of the HSPA1B (rs1061581), IL17A (rs2275913), IL10 (rs1800872), and TNF-α (rs1800629) genes of three hundred ninety eight males were studied using PCR-RFLP and real-time PCR methods, including 268 patients with VS divided into two groups: VShtv (n = 117) and VScomb (n = 151), in which VS was caused by exposure to hand-transmitted vibration (HTV) or combined exposure to HTV and whole-body vibration (COMB), respectively. The study also involved 96 patients with occupational NIHL diagnosis and 34 individuals of the comparison group without occupational contact with physical factors.&#x0D; Results. The increase in GG-HSPA1B (1267A/G) genotype frequency (p=0.058) was found in VScomb patients compared with those from the VShtv group. There was a significant difference in carriers of the C/C genotype of the IL10 (rs1800872) polymorphic locus in the group of NIHL patients relative to the comparison group (p=0.036). The results of regression analysis indicate the carriage of the A allele to reduce the risk of NIHL development.&#x0D; Limitations. The limitations include the number of examined cases in all groups, especially in comparison group and the lack of groups of workers with no occupational exposure to a physical factor. &#x0D; Conclusion. The obtained results expand the understanding of the genetic features able to determine sensitivity to the physical factors exposure that define the development of occupational pathology and the issues to be resolved at the next stage of research.

Sex-differences in the association of interleukin-10 and interleukin-12 variants with the progression of hepatitisB virus infection in Caucasians.

Interleukin (IL)-10 and IL-12 contribute to immune responses against hepatitisB virus (HBV) infection. Polymorphisms in the IL-10 and IL-12A genes might affect the clinical outcome of HBV infection. We evaluated the association of IL-10 rs1800896 and rs3024490, and IL-12A rs568408 and rs2243115 with the progression of HBV infection and development of severe liver disease stages in a white European population. A total of 636 white European patients with chronic HBV infection, 239 individuals with spontaneous HBV surface antigen seroclearance, and 254 healthy controls were enrolled. The chronic HBV infection group included patients with hepatitisB envelope antigen (HBeAg) negative chronic hepatitisB (n=255), with HBeAg positive chronic hepatitisB (n=99) and with HBeAg negative HBV infection (n=228). A total of 104 chronically infected patients were diagnosed with liver cirrhosis. Serum levels of cytokines were measured in patients with HBV infection (n=195) and in healthy controls (n=160). In adjusted multivariate analysis, the IL-10 rs1800896 AG/GG genotypes were significantly associated with an increased probability of HBV surface antigen seroclearance (OR=1.75, 95% CI 1.04-2.94, p=0.034), with an increased likelihood of HBeAg negative chronic infection (OR=1.93, 95% CI 1.05-3.54, p=0.034) and with increased serum cytokines levels in female patients. In contrast, the IL-12A rs568408 AG/AA genotypes were independently associated with an increased risk to develop liver cirrhosis, with an OR of 1.90 (95% CI 1.07-3.39, p=0.029) in male patients. The current study shows a sex-related association of the IL-10 single-nucleotide polymorphism rs1800896 and IL-12A single-nucleotide polymorphism rs568408 with different stages of HBV infection and with HBV-related liver cirrhosis in white European patients.

Genetic markers of children asthma: predisposition to disease course variants.

Asthma is a heterogeneous and often difficult to treat condition that results in a disproportionate cost to healthcare systems. Children with severe asthma are at increased risk for adverse outcomes including medication-related side effects, life-threatening exacerbations, and impaired quality of life. An important therapeutic focus is to achieve disease control, which is supposed to involve a personalized approach to treatment of asthma of any severity. Asthma is a multifactorial disease with a significant genetic determinant, however, the inheritance of asthma has not been fully elucidated. Polymorphic genes of inflammatory mediators, including cytokines, play an important role in developing various disease forms. In the current study, large-scale original data on the prevalence of cytokine gene genotypes (IL2, IL4, IL5, IL6, IL10, IL12, IL13, IL17A, IL31, IL33, IFNG, TNFA) among Russian children with asthma in Krasnoyarsk region have been obtained. Genotyping was carried out using real-time PCR. We identified markers predisposing to the development of different variants of the course of childhood asthma: the CT genotype and T allele of IL4 rs2243250 are associated with asthma (p < 0.05), especially in mild asthma and in controlled asthma. The TT genotype and allele T of IL13 rs1800925 are associated with severe and uncontrolled asthma (p < 0.05). The AA genotype of IL17A rs2275913, the TT genotype of IFNG rs2069705 and allelic A variants of TNFA rs1800629 are associated with mild asthma, and the TT genotype of IFNG rs2069705 is additionally associated with controlled asthma. The results obtained will supplement information on the prevalence of polymorphic variants of the cytokine genes in the Russian population and in asthma patients with different disease courses, which is likely to be used in order to shape a plan for Public Health Authority to prevent the development of severe uncontrolled asthma and to optimize personalized therapy.

Association of IL-17A rs2275913, IL-23R rs11209026 polymorphisms and serum level of IL-17A with rheumatoid arthritis in Egyptian patients

Several studies have reported genetic polymorphisms at the IL-23/IL-17 axis linked to rheumatoid arthritis (RA) in many populations. We aimed to investigate the association of IL-17A rs2275913 and IL-23R rs11209026 polymorphisms with susceptibility to RA and, disease clinical features and the serum level of IL-17A in Egyptian patients. This case-control study included 94 RA cases and 74 controls. TaqMan genotyping assays were used for detection of gene polymorphism and the enzyme-linked immunosorbent assay was used to quantify IL-17A serum level. There was significant difference between RA patients and controls in genotypic distribution and allelic frequency of IL-17A rs 2275913 (p &lt;0.0001). The GG genotype had 7 times higher risk for RA development (OR=7.04: 95% CI 2.11:23.46, p value= 0.001). Also, GG genotype was associated with higher level of serum IL-17 A compared to GA and AA genotypes (p&lt;0.0001). Moreover, patients carrying the GG genotype had higher disease activity score 28 (DAS28) score (4.99±0.84) compared to patients with GA (2.73±0.52, p&lt;0.0001) and patients with AA genotypes (2.67±0.41, p&lt;0.0001). Genotypic distribution of IL-23R rs11209026 was significantly different between RA patients and controls (p &lt;0.0001), but there was no difference between the allelic frequency in both groups (p=0.08). IL-23R rs11209026 SNP was not a risk for RA development. However, DAS28 was lower in AA genotype than AG and GG genotypes (p=0.002, p=0.009 respectively). The mean serum IL-17A level was higher among the RA patients (39.07±10.47 pg./ mL) compared to controls (15.23±1.88 pg/ mL; p &lt;0.0001). Also, there was a positive correlation between IL-17A serum level and DAS28 score (Spearman r = 0.42; p value &lt;0.0001). We concluded that the variant IL-17A (rs2275913) genotype could be a risk factor for RA in our population and IL-17A may play a crucial role in the development and pathogenesis of RA.

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.

A Meta-Analysis of the Association Between Genetic Polymorphisms in IL-12, IL-17, and IL-21 and Risk of Hepatitis B Virus Infection.

Cytokine imbalance is an important feature in the occurrence and outcome of hepatitis B virus (HBV). Single nucleotide polymorphisms (SNPs) within cytokine genes may affect the protein expression and eventually contribute to the susceptibility of HBV infection. The association between interleukin (IL)-12, IL-17, or IL-21 and the risk of HBV infection has been extensively studied, but yielding equivocal results. The aim of this meta-analysis was to determine the impact of SNPs in IL-12, IL-17, and IL-21 on the risk of HBV infection. We retrieved studies evaluating whether SNPs in IL-12, IL-17, and IL-21 influenced HBV infection from electronic databases, including PUBMED, Web of Science, EBOCO, OVID, and Embase. Summarized odds ratios (ORs) and confidence intervals (CIs) were calculated using STATA software. Under a homozygous comparison, the IL-12A rs568408 was associated with an increased risk of HBV infection in both overall analysis (OR = 1.68, 95% CI, 1.12-2.53) and Caucasians (OR = 1.80, 95% CI, 1.14-2.84). Under a dominant genetic model, the similarly higher risk was also observed in overall analysis (OR = 3.62, 95% CI, 3.08-4.24), Caucasians (OR = 3.29, 95% CI, 2.67-4.05), high-quality studies (OR = 3.29, 95% CI, 2.61-4.14), and low-quality studies (OR = 3.95, 95% CI, 3.17-4.93). Although no significant association was observed between IL-17A rs2275913 and the risk of HBV infection in overall comparison, subgroup analysis revealed that the IL-17A rs2275913 AA genotype was associated with a reduced risk in Asians (OR = 0.72, 95% CI, 0.57-0.91) and high-quality studies (OR = 0.71, 95% CI, 0.55-0.92). However, no significant association of IL12B rs3212227, IL-17A rs2275913, IL-21 rs2221903, and rs907715 with HBV infection was observed. In conclusion, we provide evidence that IL-12A rs568408 was associated with an increased risk of HBV infection and IL-17A rs2275913 AA genotype was a protective factor against HBV infection in Asians.

Single Nucleotide Polymorphisms in IL-1A RS1800587, IL-1B RS1143634 and Vitamin D Receptor Rs731236 in Stage III Grade B/C Periodontitis.

The purpose of the study is to determine the prevalence of interleukin (IL)-1A (rs1800587), IL-1B (rs1143634) and vitamin D receptor (VDR) (TaqI, rs731236) gene polymorphisms in the Turkish population and their association with Stage III Grade B/C periodontitis. Systemically and periodontally healthy individuals (N = 100) and Stage III Grade B/C periodontitis patients (N=100) based on clinical and radiographic examination were included in this research. Clinical attachment level, probing depth, bleeding on probing, plaque and gingival indices of the subjects were measured. Genotyping of IL-1A (rs1800587), IL-1B (rs1143634) and VDR (rs731236) polymorphisms was conducted by Real Time PCR. Allelic and genotypic distributions of IL-1A (rs1800587) gene polymorphism were not associated with periodontitis (p>0.05). In IL-1B (rs1143634) gene polymorphism, the C allele was detected more frequently in healthy individuals compared with the periodontitis patients (p=0.045). CC genotype and C allele in VDR (rs731236) gene polymorphism was higher in periodontitis patients (p=0.031, p=0.034, respectively). In comparison with Grade B periodontitis patients and healthy subjects, CC genotype and C allele were observed more frequently in the Grade B periodontitis in terms of alleles (C/T) and genotypes for VDR (rs731236) polymorphism (p=0.024, p=0.008, respectively). This study presents that the VDR (rs731236) polymorphism are associated with enhanced susceptibility to Stage III periodontitis in the Turkish population. Furthermore, VDR (rs731236) polymorphism may be used as an identification criteria to discriminate Grade B and Grade C in Stage III periodontitis.

Gene polymorphism in IL17A and gene-gene interaction in the IL23R/IL17A axis are associated with susceptibility to coronary artery disease

AimsStudies have confirmed that the IL-23R/IL-17A axis plays an important role in the development of autoimmune and inflammatory diseases. However, its role in coronary artery disease (CAD) remains unclear. Here, we conducted a large sample case-control study to investigate the association between the IL23R/IL17A axis and CAD in the Chinese Han population. MethodsTwo SNPs, rs2275913: G>A (IL17A) and rs6682925: T>C (IL23R), were genotyped in 3042 CAD cases and 3216 controls using the high-resolution melt technology (HRM). Logistic regression analyses were used to adjust the traditional risk factors for CAD and perform the gene interaction analyses. Multiple linear regression analyses were used to study the relationships between the selected SNPs and the levels of serum lipids. In addition, meta-analysis also was performed for the association between rs6682925 and rs2275913 with CAD in different popolations. ResultsOur case-control and meta-analysis for single SNPs demonstrated that the frequencies of the alleles and the distribution of the genotypes had no significant differences in CAD cases compared with controls. In the stratified analysis, we observed that the frequency of the IL17A rs2275913-A allele was more epidemic in early-onset CAD than in the controls (Padj = 0.005, OR = 1.209, 95% CI: 1.059–1.382), and the minor allele C of rs6682925 was associated with a decreased level of serum total cholesterol under a recessive model (Padj = 0.011). We demonstrated a significant interaction between rs6682925 and rs2275913 and CAD in the Chinese Han population. Four genotypes (CTGG, CCAA, CCAG, CCGG) were significantly associated with CAD (Padj = 2.94 × 10−4, OR = 0.619, 95% CI: 0.478–0.803; Padj = 0.01, OR = 1.808, 95% CI: 1.152–1.869; Padj = 6 × 10−6, OR = 2.179, 95% CI: 1.558–3.049; Padj = 0.001, OR = 1.883, 95% CI: 1.282–2.762, respectively). ConclusionOur study found no single SNP of rs2275913 in IL17A and rs6682925 in IL23R was associated with CAD in the Chinese population, but the interaction of them were significantly associated with CAD susceptibility, highlighting the key role of the IL-23R/IL-17A axis in the development of CAD. In addition, we also found rs2275913 was associated with early-onset CAD and rs6682925 was associated with total cholesterol levels, which will contribute to the clinical stratified management of this common disease.