IL-17F Gene Research Articles

Role of gene polymorphism of IL-4 and IL-17 in recurrent miscarriage, came in art cycles

Most researchers suggest that more than 50% of pregnant women after use of assisted reproductive technologies (ART) are faced with the problem of miscarriage, especially in the first trimester. The aim of the study was to investigate the frequency of genotypes and allelic variants of the IL-4 (S589T and S33T), IL-4R (Q576R), IL-17A (G197A) and IL-17F (488T/C) genes, depending on the reproductive status and assessment of their association with recurrent miscarriage, which occurred in ART cycles. Peripheral blood of 240 patients – the eastern Slav with habitual miscarriage, came in ART cycles, and 100 apparently healthy fertile women in the control group with a history of at least one term delivery and lack of spontaneous abortion episodes was studied. The groups were representative of age. DNA for molecular genetic studies of nuclei isolated from peripheral blood lymphocytes. The method is based on the destruction of lymphocytes using lysis buffer without affecting the integrity of the membranes of lymphocytes nuclei. For typing single nucleotide polymorphisms of IL-4 immune response, IL-4R, IL-17A and IL-17F using polymerase chain reaction product with the melting reaction in the presence of “adjacent” oligonucleotides. It was found that the genotype CT-33 (OR 3.99; 95% CI 2,42–6,57) and CT-589 (OR 3.99; 95% CI 2,42–6,57) gene IL-4; genotype GG576 (OR 5.95; 95% CI 1,39–25,58) gene IL-4R and TT488 genotype (OR 2.33; 95% CI 1,39–3,91) and CC488 (OR 2.27; 95% CI 0,76–6,84) IL-17F gene were associated with a significant increase in the risk of miscarriage. On the other hand, no significant differences were found between the control group and the basic frequency of polymorphisms IL-17A-G197A (rs227593). The results of the molecular-genetic typing it possible to identify in the Eastern Slavic population of residents of Odesa region of Ukraine immunogenetic markers of susceptibility/ resistance to the development of recurrent miscarriage. It is shown that cytokine gene typing can be used as a method of early diagnosis and pregravid prognosis of immune forms of reproductive loss in women.

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.

Association of IL17A and IL17F genes with rheumatoid arthritis disease and the impact of genetic polymorphisms on response to treatment

BackgroundPrevious studies have reported an association between polymorphisms in Il17A and IL17F genes and the prevalence of rheumatoid arthritis (RA) in Caucasian populations. The aim of the current study was to investigate that polymorphisms in both genes may affect RA susceptibility in the Tunisian population and to study the relation between serum IL-17 levels and synovial fluid (SF) levels and risk in RA patients. We suggested also that these polymorphisms may influence response to treatment in Tunisian RA patients. MethodsWe studied IL17A-152 G/A (rs2275913), IL17F 7488 A/G (rs763780) and IL17F 7383 A/G polymorphisms in a Tunisian population. The genotypic and allelic distributions of IL-17A and IL-17F genes polymorphisms were analyzed by Polymerase Chain-Reaction (PCR) and Restriction Fragment Length Polymorphism (RFLP) for 108 patients and 202 healthy controls.IL-17 levels were measured in synovial fluid (SF) and in serum of both 108 patients and 47 controls (pg/ml) using enzyme-linked immunosorbent assay (ELISA) technique. ResultsOur results indicated that IL17F 7488 A/G and IL17F 7383 A/G polymorphisms were significantly associated with RA risk in the whole population. However, IL17A-152 G/A polymorphism did not show any significant association with RA prevalence in the Tunisian population. Stratification according to demographic and clinical features revealed differential significant associations of IL17A-152 G/A, IL17F 7488 A/G and IL17F 7383 A/G polymorphisms within different subgroups and subtypes of clinical-pathologic features in RA patients. IL17A-152 G/A polymorphism was associated with an enhanced response to biologic and MTX treatment. IL17F 7383 A/G polymorphism was associated with an enhanced response to biologic treatment. The IL17F 7488 A/G polymorphism decreased significantly good response to biologic treatment, but enhanced response to MTX treatment. The expression of IL-17 in serum and synovial fluid (SF) in RA patients was significantly higher than that observed in healthy controls (P<0.0001) and their levels depend on RA severity. The mean IL-17 levels in the anti-TNF α treated patients decreased significantly at 0 week, 14 weeks and 30 weeks (P=0.0032 and P<0.0001, respectively). ConclusionsOur results confirmed IL17A and IL17F as potential candidate genes involved in RA. They play pivoting roles in the susceptibility and in clinical features of RA disease. Responses to RA treatments are differently conditioned by polymorphisms in IL17A and IL17F genes.

Novel SNPs in IL-17F and IL-17A genes associated with somatic cell count in Chinese Holstein and Inner-Mongolia Sanhe cattle

BackgroundBovine mastitis is the most common and costly disease of lactating cattle worldwide. Apart from milk somatic cell count (SCC) and somatic cell score (SCS), serum cytokines such as interleukin-17 (IL-17) and interleukin-4 (IL-4) may also be potential indicators for bovine mastitis. The present study was designed to investigate the effects of single nucleotide polymorphisms (SNPs) in bovine IL-17F and IL-17A genes on SCC, SCS and serum cytokines in Chinese Holstein and Inner-Mongolia Sanhe cattle, and to compare the mRNA expression variations of the cows with different genotypes.ResultsA total of 464 lactating cows (337 Holstein and 127 Inner-Mongolia Sanhe cattle) were screened for SNPs identification and the data were analyzed using fixed effects of herd, parity, season and year of calving by general linear model procedure. The results revealed that SNP g.24392436C > T in IL-17F and SNP g.24345410A > G in IL-17A showed significant effects on SCC and IL-4 in Holstein (n = 337) and on IL-17 and IL-4 in Sanhe cattle (n = 127). The homozygous GG genotype of SNP g.24345410A > G had significantly higher mRNA expression compared with the heterozygous AG genotype.ConclusionsThe results indicate that IL-17F and IL-17A could be powerful candidate genes of mastitis resistance and the significant SNPs might be useful genetic markers against mastitis in both dairy and dual purpose cattle.

IL17A and IL17F Gene Polymorphism Association with Psoriasis Risk and Response to Treatment in a Polish Population

Background: Recent studies have revealed the pivotal role of Th17 cells and interleukin-17 (IL-17) in plaque psoriasis development and treatment outcome. The IL-17 family consists of 6 structurally related cytokines (IL-17A, IL-17B, IL-17C, IL-17D, IL-17E, IL-17F), of which IL-17A and IL-17F mediate similar biological effects. Objectives: The aim of this study was to evaluate an association between the IL17A (-197G>A; rs2275913) and IL17F (rs763780: T>C; rs11465553: G>A; rs2397084: T>C) polymorphisms with psoriasis susceptibility as well as response to topical and combined topical with narrow-band ultraviolet B (NB-UVB) therapy in a Polish population. Methods: Association study involving 407 psoriasis patients and 205 healthy controls. Treatment efficacy was analyzed in 207 patients with mild psoriasis (Psoriasis Area and Severity Index; PASI 3-12) and moderate psoriasis (PASI 12-18), who were randomly subjected to topical or combined topical and NB-UVB treatment. The polymorphisms were evaluated by RT-PCR. Results: No statistically significant differences between psoriasis patients and controls were found in the frequency of the evaluated IL17A and IL17F genotypes and haplotypes. The IL17A or IL17F polymorphisms were not associated with treatment outcome measures: efficacy of treatment at the eighth week of the study and PASI change after topical or combined topical and NB-UVB therapy. However, IL17F rs2397084 variant allele C carriers required a significantly higher number of NB-UVB irradiations in comparison to TT homozygotes (15.5 ± 11.4 vs. 11.1 ± 11.9, p = 0.047) to produce a positive clinical response. Conclusion: It can be stated that the IL17A and IL17F polymorphisms are not markers of susceptibility to psoriasis. However, the IL17F polymorphism may affect the response to NB-UVB therapy.

IL17A and IL17F gene polymorphisms in patients with rheumatoid arthritis.

BackgroundInterleukin-17 plays important role in the pathogenesis of rheumatoid arthritis (RA). The aim of this study was to examine the associations between polymorphisms in the IL17A and IL17F genes and RA.MethodsWe examined 422 RA patients and 337 subjects as a control group. Single nucleotide polymorphism (SNP) in the IL17A (rs2275913) and IL17F (rs763780, rs11465553, rs2397084) genes were genotyped using TaqMan genotyping assays from Life Technologies Genomic.ResultsThere were no significant differences in distribution of IL17A and IL17F genotypes and alleles between RA patients and control group. There were no significant associations between IL17A and IL17F genotypes and age of disease diagnosis rheumatoid factor, erosive disease as well as extra-articular manifestations.ConclusionsThe results of this study suggest, that IL17A and IL17F gene polymorphism are not the important factors associated with susceptibility and some clinical parameters of RA in a Polish population.

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.

IL-17F Promotes Tissue Injury in Autoimmune Kidney Diseases.

The TH17 immune response has a central role in the pathogenesis of autoimmune diseases, implicating the TH17 master cytokine, IL-17A, as the critical mediator of diseases such as human and experimental crescentic GN. However, the relative importance of additional TH17 effector cytokines, including IL-17F, in immune-mediated tissue injury remains to be fully elucidated. Here, using a mouse model of acute crescentic GN (nephrotoxic nephritis), we identified CD4+ T cells and γδ T cells as the major cellular source of IL-17F in the inflamed kidney. Interventional studies using IL-17F gene-deficient mice, IL-17F-neutralizing antibodies, and adoptive transfer experiments into Rag1-/- mice demonstrated that CD4+ T cell-derived IL-17F drives renal tissue injury in acute crescentic GN. Notably, IL-17F-deficient nephritic mice had fewer renal infiltrating neutrophils than wild-type nephritic mice, and neutrophil depletion did not affect the course of GN in IL-17F-deficient mice. Moreover, in the chronic model of pristane-induced SLE, IL-17F-deficient mice developed less severe disease than wild-type mice, with respect to survival and renal injury. Finally, we show that IL-17F induced expression of the neutrophil-attracting chemokines CXCL1 and CXCL5 in kidney cells. The finding that IL-17F has a nonredundant function in the development of renal tissue injury in experimental GN might be of great importance for the development of anti-IL-17 cytokine therapies in TH17-mediated human autoimmune diseases.

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 IL-17A and IL-17F gene polymorphisms and risk of gastric cancer in a Chinese population.

We conducted a case-control study to investigate the role of interleukin-17A (IL-17A) rs2275913 G > A and IL-17F rs763780 T > C polymorphisms in the development of gastric cancer. A hospital-based case-control design was performed, and 153 patients and 207 control subjects were consecutively selected from the Third Affiliated Hospital between May 2013 and December 2014. Polymerase chain reaction-restriction fragment length polymorphism was used to genotype for IL-17A rs2275913 G > A and IL-17F rs763780 T > C. The genotypes of IL-17A rs2275913 G > A and IL-17F rs763780 T > C did not deviate from Hardy-Weinberg equilibrium (P values were 0.44 and 0.11, respectively). By unconditional logistic regression analysis, we observed that the GG genotype of rs2275913 was associated with an increased risk of gastric cancer compared to the AA genotype [odds ratio (OR) = 2.66; 95% confidence interval (CI) = 1.26-5.66]. The AG + GG genotype of rs2275913 increased the susceptibility to gastric cancer compared to the AA genotype, and the adjusted OR (95%CI) was 2.66 (1.26-5.66). Moreover, the GG genotype of rs2275913 was correlated with an elevated risk of gastric cancer when compared with the AA + AG genotype (OR = 2.15; 95%CI = 1.08-4.34). In conclusion, we found that the IL-17A rs2275913 G > A gene polymorphism was significantly associated with an increased risk of gastric cancer in co-dominant, dominant, and recessive models.

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.

Interleukin-17A rs2275913, Interleukin-17F rs763780 and rs2397084 gene polymorphisms as possible risk factors in Juvenile lupus and lupus related nephritis

There are no reports about the association of interleukin (IL)-17A and IL-17F gene polymorphism and susceptibility to pediatric systemic lupus erythematosus (pSLE). Objective: To examine the possible role of IL-17A rs2275913, IL-17F rs763780 and rs2397084 polymorphisms as risk factors for pSLE in a cohort of Egyptian children and to investigate their association with the clinico-pathological features including lupus nephritis (LN). Methods: Typing of IL-17A and IL-17F polymorphisms was done using restriction fragment length polymorphism for 115 children with SLE and 259 age- and sex-matched healthy controls. Results: No significant differences were found between pSLE patients and healthy controls for the allele and genotype frequencies of IL-17A rs2275913, IL-17F rs763780 and rs2397084 (p > 0.05). However, the combined genotype GGAGAA and the haplotype GGA had significant association with pSLE (pc = 0.042 and <0.001, respectively). The AA genotype of IL-17F rs763780 is more frequent in female patients (p = 0.002) and the AA genotype of IL-17F rs2397084 is more associated with positivity of ds-DNA (p = 0.007). No more associations were found for the demographic and clinical data of pSLE patients including risk of LN development, risk of non-remission, overall survival, activity and chronicity indices. Conclusion: The GGAGAA combined genotype and the GGA haplotype of IL-17A rs2275913, IL-17F rs763780 and rs2397084 can be considered risk factors for the development of SLE in Egyptian children. IL-17A rs2275913, IL-17F rs763780 and rs2397084 are not related to the LN development, SLE disease activity or overall survival.

Association study between IL-17A and IL-17F gene polymorphism and myasthenia gravis in Chinese patients.

Alleles of IL-17A and IL-17F genes were reported to be associated with many inflammatory and autoimmune disorders in Asian patients. Serum level and mRNA of IL-17A in peripheral blood mononuclear cells were reported to be significantly higher in MG patients than in healthy controls. In experimental autoimmune myasthenia gravis (EAMG) animals, IL-17 may have effects on the severity of MG. This study investigated the association between four SNPs of IL-17A and IL-17F gene (rs8193036, rs2275913 and rs3748067 in IL-17A; rs763780 in IL-17F) and MG in Chinese patients. The allele frequencies were compared between 480 MG patients and 487 healthy controls, between each MG subgroup and the control group, and between each pairs of MG subgroups. Subgroups were specified by clinical features (onset age, gender, thymoma, AChRAb and muscle involvement at onset) and maximal severity during the follow-up. No associations were found between the four SNPs of IL-17A and IL-17F gene and MG in Chinese patients.

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

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

Retraction Note to: Correlation of IL-1F genetic polymorphisms with the risk of colorectal cancer among Chinese populations.

Inflammatory/immune cells have the power of infiltrating almost all human solid tumors and influencing all stages of carcinogenesis because of their stimulation of various cytokine subsets. This study aims to determine the correlation of single nucleotide polymorphisms in the IL-17F gene and the risk of colorectal cancer (CRC). One thousand patients diagnosed with CRC and a control group of 354 healthy controls were involved. Peripheral blood samples were collected. The PCR-RFLP method was used to detect the 7383A>G (rs2397084) and 7488T>C (rs763780) in the IL-17F gene. Statistical analyses were conducted with version 12.0 STATA statistical software. We found that the allele model suggested that patients carrying C allele were 1.67 times more likely to develop CRC than healthy controls (odds ratio (OR) = 1.67, 95 % confidence interval (CI) = 1.22–2.27, P = 0.001). Similarly, the homozygous and dominant models also revealed that the minor IL-17F 7488C allele conferred an increased CRC risk compared to the major T allele among our study participants (CC vs. TT: OR = 4.15, 95 % CI = 1.26–13.36, P = 0.011; TC+CC vs. TT: OR = 1.46, 95 % CI = 1.04–2.05, P = 0.027). However, all genetic models indicated that the IL-17F 7383A>G (rs2397084) polymorphism was not associated with CRC risk (all P > 0.05). The results of this study indicate that the 7488T>C (rs763780) in the IL-17F gene may be correlated with increased risk of CRC.

IL-17A and IL-17F single nucleotide polymorphisms associated with lung cancer in Chinese population.

Genetic predisposition and environmental factors impact the development of lung cancer. The aim of this study was to investigate the association of single nucleotide polymorphisms (SNPs) of the IL-17A and IL-17F genes with lung cancer risk in Chinese Han population. A total of 678 subjects were enrolled, including 320 lung cancer patients and 358 healthy controls. Six SNPs of IL-17A (rs2275913, rs3748067 and rs3819025) and IL-17F (rs763780, rs1266828 and rs12203582) were genotyped using the polymerase chain reaction (PCR) and ligase detection reaction (LDR). The distribution of IL-17A alleles and A and AA genotype for rs2275913 had a significant association with lung cancer risk (OR: 1.26, 95% confidence interval = 1.01-1.56 and OR: 2.08, 95% confidence interval = 1.311-3.31, respectively). In the subgroup analysis, people carrying homozygous variants of rs2275913 and rs12203582 were more likely to develop lung cancer both in adenocarcinoma (OR: 2.33, 95% confidence interval = 1.34-4.05; OR: 1.84, 95% confidence interval = 1.04-3.25) and advanced (OR: 2.35, 95% confidence interval = 1.46-3.80; OR: 1.74, 95% confidence interval = 1.06-2.87) groups. Although no interaction was found between variants of rs2275913 and rs12203582 and tobacco smoking (P > 0.05), smokers carrying homozygous variants of rs2275913 and rs12203582 are at high risk of lung cancer, while no relationship were found among non-smokers. No significant associations between rs3748067, rs3819025, rs763780 and rs1266828 polymorphisms and lung cancer risk were observed. Polymorphisms of both IL-17A and IL-17F may increase lung cancer risk in Chinese population, and are associated differently with subtypes of clinical-pathologic features and tobacco smoking history of lung cancer patients. SNPs of IL-17A and IL-17F predict lung cancer risk.

Association between single nucleotide polymorphisms IL17RA rs4819554 and IL17E rs79877597 and Psoriasis in a Spanish cohort.

BackgroundThe IL17 pathway plays an important role in the pathogenesis of psoriasis (PsO). ObjectivesTo determine whether the variation at the IL17 pathway genes was linked to the risk for PsO or had an effect on disease severity and the risk for Psoriatic arthritis (PsA). MethodsCross-sectional observational study of 580 psoriasis patients and 567 healthy controls who were genotyped for six single nucleotide polymorphisms (SNPs) in the IL17RA (rs4819554, rs879577), IL17A (rs7747909), IL17F (rs763780, rs2397084), and IL17E (rs79877597) genes. ResultsWe found significant higher frequencies of IL17RA rs4819554 G carriers among the patients (OR=1.33, 95%CI=1.05–1.69; p=0.017). The IL17RA rs4819554 G allele and IL17F rs2397084 TT genotype were significantly more frequent among Cw6 positive patients (p=0.037 and p=0.010, respectively). The IL17E rs79877597C allele was significantly more common among patients with severe forms of PsO (p=0.010; OR=2.42, 95%CI=1.23–4.76), and the CC genotype with the presence of arthritis (p=0.032; OR=1.50, 95%CI=1.04–2.18). ConclusionsWe identified the IL17RA rs4819554 SNP as a risk factor for PsO. The IL17E rs79877597 SNP was a modifier of the risk for PsO disease severity and PsA.

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.

Genetic Polymorphisms in the Toll-like Receptor 10, Interleukin (IL)17A and IL17F Genes Differently Affect the Risk for Tuberculosis in Croatian Population.

Proinflammatory conditions leading to activation of macrophages via interferon-γ bear an important role in host defence against intracellular bacteria such as Mycobacterium tuberculosis (Mt). Interleukin-17 plays a similar role, as it appears to be also an activator of macrophages. Recently, the TLR-10 was identified as an anti-inflammatory factor that exerts its action via association with the TLR-2 chain at the cell surface of macrophages, the latter being an Mt-binding protein. We have previously found that gene polymorphisms that either inactivate the TLR2 gene product or have a dominant-negative role are associated with tuberculosis (TB) in Croatian population. We have now extended our survey and found that single nucleotide polymorphism (SNP) in TLR10 (rs11096957) is associated with risk for TB. Homozygotes carrying the A allele are associated with predisposition to disease as analysed by the dominant model of inheritance. In contrast, SNPs in the proinflammatory IL17A and IL17F genes (rs2275913 and rs763780, respectively), found previously to correlate with the disease occurrence in Chinese population, were not significantly associated with tuberculosis in the Croatian population.