IL-17A Gene Polymorphisms Research Articles

IL17A and IL23R gene polymorphisms affect the clinical features and prognosis of patients with multiple myeloma.

Single nucleotide polymorphisms (SNPs) in interleukin 17 (IL17A) and IL-23 receptor (IL23R) are involved in the pathogenesis of many cancers and autoimmune diseases. We investigated the influence of IL17A and IL23R SNPs on the risk of developing multiple myeloma (MM) and its clinical features. We obtained genomic DNA from 120 patients with MM and 201 healthy controls and detected IL17A -197 G/A (rs2275913) and IL23R H3Q (rs1884444) genotypes using the polymerase chain reaction-restriction fragment length polymorphism method. There were no significant differences in the genotype and allele frequencies of IL17A -197 G/A and IL23R H3Q between the controls and patients with MM. Compared with the GG and GA genotypes, the IL17A AA genotype was significantly associated with lower hemoglobin levels. The IL23R HH genotype was significantly associated with higher frequency of bone lesions and plasmacytoma than the HQ and QQ genotypes. We observed significant differences in overall survival (OS) between patients treated with thalidomide and/or bortezomib and those treated conventionally. Therefore, we also examined the effect of IL17A and IL23R polymorphisms on the clinical variables and OS in patients treated with thalidomide and/or bortezomib. We observed that the IL23R HH genotype was significantly associated with poor survival compared with the QH and HH genotypes in these patients. Our findings indicate that IL17A -197 G/A and IL23R H3Q are not associated with susceptibility to MM. However, IL-17 and IL-23R polymorphisms may affect severity, bone lesions, and extra-medullary disease in patients with MM. Moreover, IL23R polymorphisms may contribute to poor prognosis in patients with MM treated with thalidomide and/or bortezomib.

Interleukin (IL)-23 Receptor, IL-17A and IL-17F Gene Polymorphisms in Brazilian Patients with Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a progressive, autoimmune disease for which the previous studies have shown that some functional polymorphisms can influence its etiology. Knowing this, the aim of this study was to investigate the association of +2199 A/C IL-23R (rs10889677), -197 G/A IL-17A (rs2275913), and +7488 A/G IL-17F (rs763780) gene polymorphisms with RA susceptibility and clinical features in a Brazilian population. A total of 127 RA patients and 134 healthy controls were recruited for the analyses of polymorphic variants. Genotyping was performed using RFLP-PCR. Logistic regression was used to analyze the genotype distribution of the polymorphisms. Individuals carrying the homozygous CC genotype for the IL-23R polymorphism seem to be at lower risk for RA development (OR 0.22; p=0.004), as well as those carrying the variant C allele (OR 0.56; p=0.002). For the -197 G/A IL-17A polymorphism, the wild-type genotype (GG) was significantly associated with a 3.18-fold (OR 3.18; p=0.033) increased risk for RA. In relation to the +7488 A/G IL-17F polymorphism, no significant difference was found between RA cases and control subjects (p>0.05). Moreover, when investigating the relationship between polymorphisms and clinical features, no evidence of an association was found. Our findings suggest that the variants +2199 A/C IL-23R and -197 G/A IL-17A could contribute to RA development in the studied population. However, larger studies are needed to fully understand this genetic predisposition.

Meta-Analysis of Risk Association Between Interleukin-17A and F Gene Polymorphisms and Inflammatory Diseases.

This meta-analysis examined the relationship between IL-17A (rs2275913) and IL17F (rs763780 T/C) gene polymorphisms and the risk of inflammatory diseases, including periodontitis, rheumatoid arthritis (RA), and inflammatory bowel disease. PubMed, MEDLINE, EMBASE, Web of Science, and Elsevier Science Direct were searched, and odds ratios (ORs) with 95% confidence interval (CI) were calculated to estimate the strength of the association. A total of 25 studies comprising 7,474 cases and 10,628 controls were included. Significant associations were found between inflammatory diseases and IL-17A rs2275913 A versus G allele (OR = 1.197, P = 0.033) and the GA versus GG genotype in the codominant model (OR = 1.406, P = 0.036). Our findings suggested that individuals who carry the rs2275913 A allele or GA genotype have a 20% or 41%-increased risk of inflammatory diseases compared with subjects with the G allele or GG genotype, respectively. With respect to IL-17F rs763780, the C versus T allele (OR = 1.94; P = 0.040), the TC versus TT (OR = 1.39; P = 0.041), the CC versus TT (OR = 2.71; P = 0.003), as well as the TC + CC versus TT genotype (OR = 1.83; P = 0.032) were risk factors for RA. In summary, our pooled analysis indicated that the IL-17A (rs2275913) and IL17F (rs763780 T/C) increased the RA risk.

IL17A gene polymorphisms: relationship to predisposition for chronic viral hepatitis and progression to liver cirrhosis in kazakh population

This work is the first genetic association study of a potential relationship of single nucleotide polymorphisms rs8193036 and rs2275913 located in the IL17A promoter on chromosome 6p12 to chronic viral hepatitis and its progression in Kazakh population. Evaluation of the effect of IL17A polymorphism on predisposition for chronic hepatitis B and C and its progression to liver cirrhosis. A total of 862 individuals were enrolled in the retrospective case-control association study. Among the participants, 100 patients had chronic hepatitis B and/or C and liver cirrhosis, and 341 patients had chronic viral hepatitis only. Four hundred twenty-one (421) healthy HBV- and HCV-negative donors without liver diseases were recruited as population control. single nucleotide polymorphisms rs8193036[T/C] and rs2275913[G/A] were genotyped by TaqMan assays using genomic DNA extracted from peripheral blood cells. Results. Minor allele frequencies of rs8193036[C] and rs2275913[A] in the groups of patients were very similar to those observed in the control population, 0.4 and 0.3, respectively. Multivariate logistic regression analysis revealed odds ratios close to 1.0 and confidence intervals overlapping with the value of 1.0 and statistical significance p > 0.4 for any groups under comparison in the multiplicative model of inheritance. No significant association between two single nucleotide polymorphisms, rs8193036 and rs2275913 in the IL17A promoter, and susceptibility to chronic viral hepatitis C and/or B and disease progression to liver cirrhosis in Kazakh population were found.

Association between IL17A and IL17F polymorphisms and risk of Henoch-Schonlein purpura in Chinese children.

Previous studies suggested that interleukin-17 and Th17 cell play an important role in the pathogenesis of childhood Henoch-Schonlein purpura (HSP). The purpose of our study is to elucidate whether the IL17A and IL17F gene polymorphisms are susceptibility genes for the development of HSP in Chinese children. A total of 148 HSP patients and 202 controls were enrolled for analyzing the single nucleotide polymorphisms (SNP) of IL17A (rs2275913, rs8193037 and rs3819025) and IL17F (rs763780 and rs9463772). TaqMan Real-Time polymerase chain reaction method was used in SNP genotyping. Compared to the healthy controls, the IL17A rs2275913 variant allele A showed a significant association with HSP [odds ratio (OR) 0.70; 95% CI 0.51-0.94, P=0.018]. Genotyping analysis demonstrated rs2275913 was associated with a decreased HSP risk (G/A vs. G/G: OR 0.56; 95% CI 0.33-0.95; A/A vs. G/G: OR 0.46; 95% CI 0.24-0.86; P=0.032). Also, our findings showed that the A allele of IL17A rs3819025 was associated with a higher risk of HSP nephritis (OR 1.61; 95% CI 1.00-2.58; P=0.047). In addition, a risk haplotype of IL17A (GGA) was found (OR 1.84; 95% CI 1.17-2.88; P=0.008). However, no significant differences between HSP patients and healthy controls were observed when comparing genotype, allele or haplotype frequencies of the IL17F rs763780 and rs9463772 polymorphisms. In this study, we confirmed that the rs2275913 polymorphism of the IL17A gene was associated with susceptibility to HSP in Chinese children. However, there was no relationship between IL17F rs763780 and rs9463772 polymorphisms and HSP susceptibility.

Assessment of the Effects of IL9, IL9R, IL17A, and IL17F Gene Polymorphisms on Women with Allergic Rhinitis in Shahrekord, Iran.

Background:The genes encoding IL9, IL9R, IL17A, and IL17F have recently been implicated in the genetic basis of rhinitis and allergy.Aim:The purpose of this study was to assess the association of the single nucleotide polymorphisms (SNPs) of IL9, IL9R, IL17A, and IL17F and potential interaction of these genes with the determination of IgE levels in women with allergic rhinitis (AR) in Shahrekord, Iran.Subjects and Methods:In a case–control study, SNPs from the IL9, IL9R, IL17A, and IL17F were genotyped in 394 random samples including 195 AR patients and 199 normal controls. Enzyme-linked immunosorbent assay was performed for the determination of serum total IgE levels. The Student's t-test was used to compare the differences. The Chi-square test was performed to compare proportions of cases with different clinical features among cases with different genotypes. The genotype and allele frequencies were obtained by direct counting. Hardy–Weinberg equilibrium was tested between cases and controls separately. The relative risk associated with rare alleles was estimated as an odds ratio with 95% confidence interval. P ≤ 0.05 was considered statistically significant.Results:The rs731476 SNP in the IL9R was significantly associated with the AR phenotype in women. No association was found between any of the other SNPs in IL9, IL17A, and IL17F genes and AR. In the gene–gene interaction analysis, we found that IL9R/IL9 genotype rs731476 T-/rs2069885 G conferred a higher risk for AR phenotype development. We also did not find a significant association in terms of IgE levels between cases and controls.Conclusion:Our result suggests that the rs731476 SNP located in the IL9R is associated with an increased susceptibility to AR in females. In a subsequent gene–gene interaction analysis, the rs731476 T-/rs2069885 G-genotype combination (IL9R/IL9) has significantly been associated with the development of the AR phenotype.

Association between interleukin-17A polymorphism and coronary artery disease susceptibility in the Chinese Han population.

Coronary artery disease (CAD) is a major global health problem. In China, the incidence of CAD and the rate of mortality arising from it have increased every year. Interleukin-17A (IL-17A) is a proinflammatory cytokine produced by activated T cells, and it may be involved in the development of CAD. Genetic polymorphisms in functional regions of the IL17A gene have a plausible role in modulating the risk of CAD. To evaluate the role of IL17A polymorphisms as a risk factor for CAD, we performed a detailed analysis of possible functional single nucleotide polymorphisms (SNPs) in regulatory regions of IL17A. This study examined the potential association between CAD and five SNPs (rs8193037, rs8193036, rs3819024, rs2275913, and rs3748067) of the IL17A gene. The allelic or genotypic frequencies of the rs8193037 (promoter region) and rs8193036 (promoter region) polymorphisms in CAD were significantly different from those in healthy controls. The CAD subjects had a significantly lower frequency of the A allele of rs8193037 (P = 0.009, OR = 1.772, 95%CI = 1.146- 2.742) and the T allele of rs8193036 (P = 0.010, OR = 1.754, 95%CI = 1.139-2.701). Strong linkage disequilibrium was observed in one block (D' > 0.9). Significantly fewer T-G-G-A haplotypes (P = 0.045) were found in CAD subjects in block 1. These data suggest that IL17A gene polymorphisms confer susceptibility to CAD, and support the notion that dysfunction of IL-17A is involved in the pathophysiological process of CAD.

Influence of the IL17A and IL17F gene polymorphisms on the long-term kidney allograft function and return to dialysis after kidney transplantation.

The immune response after allogenic transplantation is a complex phenomenon involving cytokines, chemokines, and other mediators of inflammation. The aim of this study was to evaluate the influence of the IL17A and IL17F gene polymorphisms on long-term kidney allograft function, graft function loss/return to dialysis, and mortality after kidney transplantation. This study enrolled 269 Caucasian deceased donor renal transplant recipients. The rs2275913:G>A (-197G>A) polymorphism within the IL17A gene promoter and rs2397084:T>C (Glu126Gly), rs11465553:G>A (Val155Ile), and rs763780:T>C (His167Arg) polymorphisms within the IL17F gene were genotyped. Creatinine concentrations 12, 24, 36, 48, and 60 months after transplantation were significantly higher in recipients with the rs2275913:A>G IL17A GG genotype (GG vs. GA + AA: p = 0.03, p = 0.004, p = 0.006, p = 0.03, p = 0.04, respectively). Moreover, the GG genotype was statistically significantly associated with increased risk of delayed graft function. This association remained significant in multivariate regression analysis adjusted for recipients' age and sex. In the case of the rs11465553, IL17F univariate Cox regression analysis showed statistically significant association of GA genotype with higher risk of graft loss/return to dialysis (GA vs. GG: HR = 2.795, 95%CI = 1.031-7.579, p = 0.04). The results of our study suggest that the GG genotype of the rs2275913 IL17A gene promoter polymorphism is associated with significantly impaired long-term kidney allograft function, whereas the GA genotype of the rs11465553 IL17F gene polymorphism may be associated with a significantly higher risk of graft function loss and return to dialysis after kidney transplantation.

Association of IL-17A and IL-17F gene polymorphisms with chronic hepatitis B and hepatitis B virus-related liver cirrhosis in a Chinese population: A case-control study

Interleukin (IL)-17 has been shown to play an important role in tissue inflammation and in the pathogenesis of immune-related liver damage. Genetic variations in IL-17 gene may be associated with the development of hepatitis B virus (HBV) infection. However, literature is scanty regarding their association. We conducted a case-control study including 433 subjects (171 healthy controls, 130 patients with chronic hepatitis B [CHB]; and 132 patients with HBV-related liver cirrhosis [HBV-LC] to assess the association between IL-17A rs4711998, IL-17A rs2275913 and IL-17F rs763780 polymorphisms and risk of CHB and HBV-LC. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing. Our results revealed a statistically significant association between IL-17A rs4711998 G allele and increased risk of HBV-LC risk (OR=1.541, 95% CI 1.057-2.246, P=0.025). Subjects carrying the IL-17A rs4711998 AG genotype were 1.75 times more likely to develop HBV-LC (OR=1.757, 95% CI 1.096-2.817, P=0.026). Stratification analysis indicated that IL-17A rs4711998 G allele and AG genotype enhanced the risk of HBV-LC development among men and older age (≥50years) subject groups. In addition, we found that GCT haplotype also might be a risk factor for HBV-LC (OR=2.448, 95% CI 1.137-5.271, P=0.019). Furthermore, no significant association between IL-17A rs2275913 and IL-17F rs763780 polymorphisms and CHB, HBV-LC risk was observed (P>0.05). Our data provide the first evidence that the IL-17A rs4711998 genetic variant may contribute to HBV-LC susceptibility in a Chinese population.

Investigation of the role of IL17A gene variants in Chagas disease.

Human host genetic factors have been suggested to be determinants of the prevalence and clinical forms of Chagas disease. In this regard, IL-17A is believed to control parasitemia and protect against heart disease. In this work, we assessed whether IL17A gene polymorphisms are related to infection and/or development of the cardiac form of Chagas disease by genotyping for five IL17A SNPs (rs4711998, rs8193036, rs3819024, rs2275913 and rs7747909) in 1171 individuals from a Colombian region endemic for Chagas disease, classified as seronegative (n=595), seropositive asymptomatic (n=175) and chronic Chagas cardiomyopathy (n=401). Our results showed that SNP rs8193036, which is located upstream of the coding region of the gene, was slightly associated with protection against T. cruzi infection (P=0.0170, P(FDR)=0.0851, odds ratio (OR)=0.80, confidence interval (CI)=0.66-0.96) and associated with protection against the development of cardiomyopathy (P=0.0065, P(FDR)=0.0324, OR=0.75, CI=0.60-0.92). This finding suggests that this IL17A polymorphism could be associated with Trypanosoma cruzi infection and the development of chronic cardiomyopathy due to differential expression of cytokine IL-17A.

IL-17A and IL-17F gene polymorphisms in patients with rheumatoid arthritis

IL-17A and IL-17F gene polymorphisms in patients with rheumatoid arthritis

Multiple sclerosis and susceptibility to cardiovascular diseases: Implications of ethnicity-related interleukin-17A gene polymorphism?

There are conflicting findings on whether patients with MS are at more or less risk of vascular comorbidities as compared to the general population. The worldwide incidence and prevalence of cardiovascular diseases (CVD) in the MS patients has been reported to vary substantially by region. Inflammation and demyelination in MS seem to be due to an autoimmune process mediated by IL17 secreting Th17 cells. Genotypic and allelic frequencies of IL17A and IL17F gene polymorphisms seem to confer risk to MS across populations. Increased serum levels of TH17 cells and IL-17 have been connected with atherogenesis. Ethnic-specific IL17A gene haplotypes have been associated with the risk of developing atherosclerosis and premature coronary artery disease. The co-occurrence of CVD with MS might be due to ethnicity-related IL-17 gene polymorphism implying geographic and population heterogeneities. Ethnic-specific IL17 gene polymorphism may explain the conflicting results both on the roles of IL17 and Th17 cells in atherosclerosis development and about the epidemiology of CVD in MS population across countries. Genomic and proteomic studies are required to assess the possibility to use polymorphisms of IL17 gene as biomarkers of racial susceptibility to CVD in MS.

Investigating the Association of IL-17A and IL-17F with Susceptibility to Pre-eclampsia in Iranian Women.

Pre-eclampsia (PE) is one of the most important and life-threatening pregnancy disorders that affect at least 3-5% of all pregnancies. Imbalance in helper T cell functions may play a role in predisposing to PE or severity of the disease. Elevated frequencies of Th17 cells in the peripheral blood of PE patients have been reported. Several single nucleotide polymorphisms (SNP) within IL-17 gene have been identified that may affect the IL-17 production. To investigate the association between IL-17A (-197A/G) and IL-17F (+7488T/C) gene polymorphisms and susceptibility to PE in a group of Iranian women. Moreover, to study any correlation of the polymorphisms data with the level of IL-17, at mRNA level in the paternal and maternal parts of the placentas and also at protein level in the peripheral and placental blood samples. A group of 261 PE patients and 278 age-matched healthy women with at least two previous normal pregnancies formed the cases and controls of this study. IL-17A (-197A/G) and IL-17F (+7488T/C) polymorphisms were genotyped using PCR-RFLP method. The protein level of IL-17A was assessed in the sera of 40 PE and 40 healthy women using ELISA method and mRNA expression was also measured in placental samples of 19 PE and 19 control women using Q-PCR technique. Statistical analysis indicated that there were no differences in genotype, allele or haplotype frequencies regarding the studied SNPs between cases and controls. The level of IL-17A was elevated in the placental blood and the fetal tissue at protein and mRNA levels (p< 0.009 and p<0.000, respectively) in PE as compared with the healthy women. The effect of IL-17 cytokine in pre-eclampsia is not due to the studied cytokine polymorphisms but local production of IL-17 might have an effect on the predisposition to the disease.

Interleukin-17FT7488 allele is associated with a decreased risk of colorectal cancer and tumor progression

BackgroundIL-17 family of cytokines and human IL-23R play important and sometimes contradictory roles in autoimmune and inflammatory diseases as well as human malignancies. Different alleles of this cytokine family may differentially affect IL-17 secretion. We sought to investigate the association of IL-17A, IL-17F and IL-23R gene polymorphisms with the susceptibility to colorectal cancer (CRC). MethodsThe IL-17A rs2275913 (G197A), IL-17F rs763780 (T7488C), IL-23R rs11209026 and IL-23R rs1088967 SNPs were detected in 202 patients with colorectal cancer and 203 healthy age/sex matched controls by PCR-RFLP method. For evaluation of the functional relevance of these SNPs with IL-17A and IL-17F production, the serum levels of IL-17A and IL-17F were investigated in 107 and 109 patients as well as 33 and 52 healthy individuals, respectively, by ELISA assays. ResultsThe IL-17F TT genotype [OR=0.44, 95% CI: 0.21–0.94, P=0.03] and T allele [OR=0.46, 95% CI: 0.21–1.1, P=0.03] were associated with a decreased risk of CRC compared with the TC genotype and C allele. Moreover, IL-17F TT genotype was significantly associated with well differentiation in tumors (P=0.02). We also observed a significant association between the AG genotype of IL-17A G197A SNP with increased risk of colorectal cancer as compared to AA genotype (P=0.001). The IL-17A concentrations in the sera of patients with CRC were significantly elevated compared to healthy individuals (P=0.008), and serum level of IL-17A was significantly related to tumor size (P=0.043). The A allele of IL-23R rs10889677 polymorphism was marginally associated with increased IL-17A levels in the sera of patients (P=0.08). The genotype distributions of IL-23R rs11209026 and IL-23R rs10889677 SNPs were not significantly different between CRC patients and controls. The haplotypes of IL-17A G197A/IL-17F T7488C and IL-23R were not significantly associated with CRC. No IL-17F was detected in the sera of patients and only one healthy individual had IL-17F in his serum. ConclusionOur findings suggest that the T allele of IL-17F T7488C polymorphism may be involved in reduced risk of CRC and IL-17A may be an attractive target for colorectal cancer immunotherapy.

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

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.

AB0762 Clinical Associations of the IL-17A, IL-17F and Nfkb-1 Gene Polymorphisms in Patients with Rheumatoid and Psoriatic Arthritis

BackgroundThe pro-inflammatory cytokines IL-17A and IL-17F, primarily produced by Th17 cells, has been shown to be involved in all stages of the autoimmune and inflammatory diseases [1]. Th17 cells are...

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

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.

May TLR4 Asp299Gly and IL17 His161Arg polymorphism be associated with progression of primary measles infection to subacute sclerosing panencephalitis?

SSPE is a progressive neurological disorder of children. Only some of the children who are infected with measles virus develop SSPE, which supports individual variation. TLR-2 and TLR-4 play an important role in innate immunity by recognizing envelope proteins of MV. Another important cytokine that plays an important role in orchestrating innate immune function is IL-17. The purpose of our study is to elucidate whether the TLR2, TLR4, IL17F and IL17A gene polymorphisms are susceptibility genes for the development of SSPE. Using the PCR-RFLP methods, the single nucleotide polymorphisms of TLR2 (Arg753Gln, Arg677Trp, -194 to -174 del), TLR4 (Asp299Gly and Thr399Ile) IL17F (His161Arg, Glu126Gly) and IL17A were studied in 54 patients with SSPE and 81 healthy controls. For Asp299Gly polymorphism of the TLR4 gene we found that there were no control individuals who were homozygous carriers of the Gly/Gly genotype, and the risk for SSPE increased at approximately 4.7 fold for the heterozygous carriers of the Asp/Gly genotype (OR 4.727, 95%-CI 1.192-18.742; P=0.01), when compared to healthy controls. Also our findings demonstrate that homozygosity for the Arg161 variant of the IL17F His161Arg polymorphism is inversely associated with development of SSPE (OR 0.114 95%-CI 0.026-0.494; P<0.001). In conclusion, it is suggested that variation in susceptibility to SSPE disease may be in part due to variations in TLR4 and IL17 function resulting from polymorphisms of TLR4 Asp299Gly and IL17F His161Arg.

Analysis of IL-17 gene polymorphisms in Chinese patients with dilated cardiomyopathy

Cardiomyopathy is one of the major causes of sudden death and/or progressive heart failure. Dilated cardiomyopathy (DCM), comprising 60% of the cases of identified cardiomyopathy, is the most common form of heart muscle disease. Interleukin 17 (IL-17) is a proinflammatory cytokine that has been implicated in the pathogenesis of various diseases. To evaluate the influence of IL-17A and IL-17F gene polymorphisms on the risk of DCM, a case-control study was conducted in a Chinese Han population. The TaqMan® SNP Genotyping Assay was used to genotype the SNP rs2275913 of IL-17A and SNP rs763780 of IL-17F in 288 DCM patients and 421 ethnicity-matched controls. No significant difference in genotypic and allelic frequencies between DCM patients and control subjects was observed. However, Results of stratified analysis revealed that rs763780 was associated with male DCM patients in a dominant genetic model (p=0.031, OR=1.83, 95% CI=1.04-3.22). Our results suggest that the tested two IL-17 SNPs, rs2275913 and rs763780, are not found to be associated with DCM in the Chinese population studied.

Evaluation of IL17A expression and of IL17A, IL17F and IL23R gene polymorphisms in Brazilian individuals with periodontitis

The IL23/Th17 axis plays an important role in the pathogenesis of cell-mediated tissue damage caused either by autoimmunity or immune responses against bacterial infection. Single nucleotide polymorphisms in the IL17A, IL17F and IL23R genes have been associated with several inflammatory diseases. However, these polymorphisms have not yet been studied in periodontitis. The aim of present study was to evaluate the expression of IL17A and occurrence of the IL17A (rs2275913), IL17F (rs763780) and IL23R (rs11209026) gene polymorphisms in different clinical forms or severity of periodontitis in a sample of Brazilian individuals. Peripheral blood was obtained from 30 non-smoker individuals and analyzed by flow cytometry to determine IL-17 expression. Genomic DNA was obtained from oral swabs in 180 individuals and analyzed by Real-time PCR. The study group was composed by individuals without periodontitis (control), with aggressive periodontitis (AP) and with chronic periodontitis (CP). Higher frequency of IL17A+CD4+ T cells was observed in control group. The A+ genotype from IL17A (rs2275913) was associated with lack of disease. No association was found considering the IL17F and IL23R polymorphisms. Our data suggest that IL17A and the presence of IL17A (rs2275913) A allele are associated with the absence of periodontal disease.