IL-17A G197A Research Articles

Associations of IL17A G-197A single nucleotide polymorphism with immunological parameters and structural changes of the brain in schizophrenia

Schizophrenia is a chronic mental disorder that is caused by a complex palette of genetic, epigenetic and environmental factors. Some of the important components of its pathogenesis are systemic inflammation and the dysfunction of immunity, which lead to neuroinflammation, contributing to development of structural brain changes. Earlier we have shown that increase in interleukin-17A levels is associated with morphometric changes and immune dysregulation in schizophrenia. IL17A G-197A (rs2275913) genetic polymorphism is involved in determining interleukin-17A secretion. The goal of this work was to investigate the associations between rs2275913 polymorphism, immune disorders and structural neurovisualization findings in schizophrenia to provide new insights into the immunopathogenesis of this disease. 60 patients aged 18 to 42 years diagnosed with schizophrenia were enrolled. 85 healthy volunteers were included into the control group. Multiplex assay was used to determine cytokine and chemokine serum levels. Rs2275913 polymorphism was assessed by polymerase chain reaction with electrophoretic detection of amplification products. A number of relationships between rs2275913 polymorphism and the immune parameters in schizophrenia were revealed. Carriers of G allele showed significant increase in IFNY, a key cytokine of Th1-link of adaptive immunity, and IL-8, an inflammatory chemokine. Also, increased levels of CXCL16 were observed in patients carrying the G allele. CXCL16 activates secretion of other proinflammatory chemokines and is involved in activation of Th1 adaptive immunity. Associations of heterozygous GA genotype with reduced cortical thickness in a number of areas of the frontal cortex in schizophrenia were found. Changes in cortical thickness in some of these areas, including middle frontal gyrus and orbitofrontal cortex, can be relevant to the pathogenesis of schizophrenia. The results highlight the importance of immunogenetic factors in the pathogenesis of schizophrenia and indicate that the rs2275913 polymorphism requires further studies as a potential biomarker of immune dysregulation and morphometric brain changes in schizophrenia.

Polymorphism of the Interleukin Genes IL-17A G197A and IL-17F A7488G in Patients with Gastric Cancer in the West Siberian Region

Polymorphism of the Interleukin Genes IL-17A G197A and IL-17F A7488G in Patients with Gastric Cancer in the West Siberian Region

From genes polymorphisms to mucosal expression of cytokines: evaluating IL-23/IL-17 axis in adult patients with gastritis.

Chronic inflammation is the typical sign of gastritis that may shift into gastric cancer. IL-17A and IL-17F as a novel inflammatory cytokines subset of CD4+Th play the main role in inflammation. A key cytokine receptor in the inflammatory IL-17/IL-23 axis, the interleukin 23 receptor (IL23R), may be related to gastritis. We evaluated the correspondence between IL-17A G197A, IL-17F A7488G and IL23R+2199 A/C polymorphisms with TGF-β1, IL-6, IL-17, IL-21 and IL-23 mucosal mRNAs expression in uninfected H. Pylori (HP) chronic gastritis patients. Total RNA and genomic DNA were separated from gastric biopsies of 44 patients with gastritis. Subsequently, mucosal mRNAs expression of TGF-β1, IL-6, IL-17, IL-21 and IL-23 were assessed by real-time PCR. To polymorphisms determination of IL-17A G197A, IL-17F A7488G and IL-23R +2199A/C the PCR-RFLP was used in gastric biopsies. Results point that IL-17A G197A, IL-17F A7488G and IL23R +2199A/C polymorphisms did not influence the mucosal expression of TGF-β1, IL-6, IL-17 and IL-21 (p> 0.05). In an opposite result, we don't find a correspondence between IL-17A G197A, IL-17F A7488G polymorphisms and mucosal expression of IL-23 (p> 0.05). In a contrary, we found a correlation between IL23R +2199A/C polymorphism and mucosal expression of IL-23 in patients with chronic gastritis (p< 0.05). These findings propose that IL23R +2199A/C polymorphism may change the mucosal expression of IL-23 pattern in patients with gastritis disease in the absence of HP, but to support the conclusion, more research may be required.

The effect of gene polymorphism of certain cytokines on echocardiographic parameters in patients with chronic rheumatic heart disease

Aim.To assess the effect of polymorphism of tumor necrosis factor-а (TNF-α) cytokines and interleukin (IL-17A, IL-17F, IL-10) on echocardiographic parameters in patients with chronic rheumatic heart disease (RHD).Material and methods. A total of 128 patients with RHD were examined, average age was 58,96±0,34 years. Echocardiography was performed on a Philips Affinity 50 machine. Genotyping was carried out using polymorphic TNF-α markers (G308A, IL-10 G1082A, IL-17A G197A, IL-17F А161Н0 by polymerase chain reaction with an electrophoretic scheme for detecting the result of “SNP-EXPRESS”.Results. RHD homozygotes for TNF-а A308A had the largest linear dimensions of the left ventricle (left ventricle end-diastolic dimension (LVED) — 5,80±0,22 cm, left ventricle end-systolic dimension (LVES) — 3,93±0,27 cm), as well as the studied homozygous for IL-17A A197A (LVED — 5,81±0,13 cm, LVES — 3,78±0,11 cm). In group of TNF-α G308G homozygotes, values of right heart (right ventricle — 2,75±0,05 cm, right atrium — 4,80±0,11 cm) were the largest and mitral valve orifice area (MVOA) was smallest — 1,52±0,04 cm2. Heterozygous patients with IL-17F Д161Н also had a greater dilatation of the ventricles compared with homozygotes of IL-17F Н161Н, in which parameters were close to normal (LVED 5,58±0,05 cm, LVES 3,68±0,04 cm). There was no statistically significant difference in linear sizes of the left and right heart in patients with IL-10 polymorphism. IL-10 polymorphism patients had statistically significant MVOA differences: minimum MVOA in G1082A heterozygotes — 1,40±0,06 cm2and maximum — 1,64±0,04 cm2in G1082G homozygotes. IL-10 G1082G homozygotes was characterized by maximum values of interventricular septum — 1,13±0,04 cm, left ventricular posterior wall — 1,10±0,03 cm.Conclusion. Homozygosity of TNF-α A308A and IL-17A A197A in RHD patients leads to the largest linear sizes of the left ventricle, and homozygosity for TNF-а G308G — to the maximum sizes of the right heart and left atrium against the background of the minimum sizes of MVOA. IL-10 polymorphism has not effect on heart linear dimensions, but IL-10 G1082G leads to maximum MVOA size.

Polymorphisms of IL-17A and IL-17F in Periodontal Disease: A Case-Control Study

Background: Increased interleukin-17 (IL-17) leads to the production of proinflammatory mediators and increases local inflammation. Interleukin-17 may also promote receptor activator of nuclear factor kappa-B ligand (RANKL) expression on gingival fibroblasts, T cells, and B cells, resulting in alveolar bone resorption. Interleukin-17A and IL-17F levels in saliva and gingival crevicular fluid (GCF), were found to be elevated in periodontitis patients. Thus, IL-17A and IL-17F polymorphisms were hypothesized to be associated with a risk of periodontitis. Methods: The present study was conducted on 60 subjects, including 20 stage II grade B periodontitis patients, 20 stage III grade C periodontitis patients, and 20 healthy controls. Blood samples were drawn from the subjects and analyzed for IL-17A G-197A and IL-17F 7488T/C genetic polymorphisms using the TaqMan assay. Results: There was a significant statistical difference between the distribution of the different genotypes and the different alleles in the three groups for IL-17A G-197A with the A allele presence indicating a risk of periodontitis. Conclusions: Interleukin-17A G-197A polymorphism is significantly associated with different clinical forms of periodontitis in the Egyptian population. The A allele could be considered a risk factor for periodontal diseases.

Association of NFKB1 -94 ins/del variants with BMI in patients with myocardial infarction

BackgroundMyocardial infarction (MI) is one of the major causes of death and disability in the world. AimWe studied the functional polymorphisms of IL17A (HGNC:5981) G197A (rs2275913; NC_000006.11:g.52051033G > A) and −94 NFKB1 (HGNC:7794) ATTG ins/del (rs28362491, NC_000004.12:g.102500998_102501001ATTG) in patients with MI. MethodsThe selected polymorphisms were assessed in 201 MI patients and 201 healthy blood donors from Fars Province. Associations between allele frequencies, serum CXCL1 levels and clinicopathological criteria of MI were examined. ResultsA significant increase in del minor allele of NFKB1 in individuals with a BMI lower than 25 (P = 0.048) and in patients who needed coronary artery bypass graft during the course of treatment (P = 0.044) was observed. Also we found a significant association between plasma content of CXCL1 and -94 NFKB1 ATTG ins/del (rs28362491) polymorphism (P = 0.01). A trend of increase in the IL17A A-allele in patients with left ventricular hypertrophy and those with apical hypokinesia was observed as well. ConclusionThe minor alleles of genes upstream and downstream of IL-17A pathway are associated with BMI and clinicopathological parameters of MI severity.

IL8 and IL17A polymorphisms associated with multibacillary leprosy and reaction type 1 in a mixed population from southern Brazil.

We evaluated the influence of the IL8 T-738A (nonidentified rs), IL8 T-353A (rs4073), IL17A G197A (rs2275913), and IL17F T7488C (rs763780) single-nucleotide polymorphisms on leprosy. The AA genotype of IL8 T-353A was observed as a risk factor for multibacillary leprosy, regardless of gender and age-of-onset of disease, considering the recessive model (OR, 3.8; 95% CI, 1.1-13.5; P, 0.023). Furthermore, the AA genotype of IL17A G197A was associated with leprosy type 1 reaction (OR, 2.4; 95% CI, 1.1-5.1; P, 0.026) when compared to the group without reaction, which was adjusted for gender and age-of-onset of disease by the model log additive. These results indicate association of IL8 and IL17A polymorphisms with the progression to multibacillary leprosy and with the type 1 reaction, respectively.

IL-17 and colorectal cancer risk in the Middle East: gene polymorphisms and expression.

BackgroundIL-17 expressed by Th17 cells play a crucial role in tissue inflammation by induction of proinflammatory and neutrophil mobilizing cytokines, and IL-17 polymorphisms are associated with colorectal cancer (CRC).ObjectiveWe investigated the expression of IL-17 and the association of IL-17 gene polymorphisms with CRC susceptibility in a Middle East population.Materials and methodsThe study included 117 diagnosed CRC patients and 100 age- and gender-matched healthy controls. IL-17A rs2275913 (G197A) and IL-17F rs763780 (T7488C) single nucleotide polymorphisms, mRNA, and protein levels of IL-17A were assessed.ResultsWe observed significant association between rs2275913 in IL-17A and susceptibility to CRC (p = 0.016228). The AG and AA genotypes conferred 2-fold and 2.8-fold, respectively, higher risk of developing CRC compared with individuals having GG genotype. Stratification of the data based on gender and age revealed very strong association of CRC with IL17A rs2275913 only in males and “AG” genotype in patients ≤57 years of age at the time of disease diagnosis. The rs763780 in IL-17F was not linked with CRCs in our cohort. Furthermore, IL-17A mRNA expression in CRCs was significantly elevated compared to adjacent normal tissues, particularly in early stages of disease (p = 0.0005). Strong immunoreactivity to IL-17A protein was observed in 70% of early stage relative to 30% of late-stage tumors.ConclusionThe IL-17A G197A variant may be utilized as a genetic screening marker in assessing CRC risk, and its expression can be used as a biomarker for early detection of CRC in the Saudi population.

IL17A polymorphism and elevated IL17A serum levels are associated with oral lichen planus.

The aim of this study was to evaluate the association of IL17A G197A polymorphism and serum levels with oral lichen planus (OLP) susceptibility and clinical presentation. Eighty-three individuals diagnosed with OLP and 99 healthy controls (C) were consecutively recruited. All participants had desquamating oral mucosal cells collected and DNA isolated for IL17A (G197A) genotyping. Blood samples of 42 OLP individuals and 23 healthy controls were collected for evaluation of IL17A serum levels. IL17A G197A genotypes were associated with an increased chance of having OLP (GA/AA×GG, OR=3.44, 95% CI=1.87-6.33, p<.001). Overall A carriers (GA or AA) were more common in OLP (38.1%) than in C (20.2%; OR=2.43, 95% CI=1.53-3.87, p<.001). Serum levels of IL17A were higher among patients with OLP than in healthy controls (reticular, p=.0003; erosive, p<.001), but no difference was found among the disease types. IL17A G197A is associated with a higher susceptibility of developing OLP and these patients seem to present a considerable increase in IL17A serum levels. These findings suggest that Th17 cells, and IL17A in particular, may play a pivotal role in OLP pathogenesis.

Association of interleukin-17 single nucleotide polymorphisms with susceptibility to osteoarthritis

Objective To test single nucleotide polymorphisms (SNP) of IL-17A G-197A and IL-17F T7488C in the Chinese Han nationality population and analyze the association of the SNP with susceptibility to osteoarthritis. Methods Two hundred patients with primary knee OA underwent total knee arthroplasty and 200 healthy individuals were recruited into this study from January 2008 to December 2015. We obtained DNA from 2 ml of whole blood for 200 OA patients (OA group) and 200 healthy (healthy control group) to employed a polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) assay to identify the genotypes IL-17A G-197A (rs2275913) and IL-17F T7488C (rs2275913). The distribution of IL-17A G-197A (rs2275913) and IL-17F T7488C (rs2275913) genotypes and allele frequencies were detected between the two groups. Chi-square test was used to compare genotype and allele frequency of IL-17A G-197A and IL-17F T7488C between the two groups. If the difference between the two groups was statistically significant, then odds ratio (OR) and 95% confidence interval (95%CI) would be calculated. Results The frequency of AA, AG and GG genotype of IL-17A G-197A(rs2275913) was 4.0%, 54.0% and 42.0% in OA group, which differed from control group (18.0%, 53.5% and 28.5%). The frequency of A and G allele were 31.0% and 69.0% in OA group, which differed from control group (44.8% and 55.3%). The risk of OA in carriers with an G allele (G/A or G/G genotypes) was statistically higher compared to that of carriers with the A/A genotype (AG: OR=0.862, 95%CI=0.729-1.019; GG: OR= 1.259, 95% CI=0.967-1.639; A:OR=0.693, 95% CI=0.577-0.831; G:OR=1.249, 95% CI=1.119-1.394). The distributions of TT, TC and CC genotypes for the IL-17F T7488C polymorphism (rs763780) in OA patients and controls shown 76.5%, 18.0%, 5.5% and 81.5%, 15.5%, 3.0%,respectively. The frequency of T and C allele were 85.5%, 14.5% and 89.3%, 10.8% in 2 group. There were no significant differences in the alleles frequency and genotypes distribution for IL-17F T7488C between OA patients and volunteers. Conclusion Polymorphism of IL-17A G-197A may be closely associated with susceptibility to the development of OA in the Chinese Han nationality population. Genotype G/A and G/G of rs2275913 is a high factor for OA while AA is a low risk factor. However, there is no relationship between rs763780 and OA susceptibility. IL-17F T7488C gene does not increase the risk of suffering from OA. Key words: Osteoarthritis, knee; Interleukins; Genetic testing; Disease susceptibility

Role of IL-17A rs2275913 and IL-17F rs763780 polymorphisms in risk of cancer development: an updated meta-analysis.

Single nucleotide polymorphisms (SNPs) in the interleukin-17 (IL-17) gene have been shown to be correlated with susceptibility to cancer. However, various studies report different results of this association. The aim of the present work was to clarify the effects of IL-17A G197A (rs2275913) and IL-17F T7488C (rs763780) polymorphisms on cancer risk. We performed systematic searches of the PubMed and CNKI databases to obtain relevant publications. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the association of rs2275913 and rs763780 polymorphisms with cancer risk. Data were extracted from the selected studies, and statistical analysis was conducted using the STATA software. Our results indicated that rs2275913 and rs763780 polymorphisms significantly increase cancer risk, especially in gastric cancers. Subgroup analysis suggested the existence of a significant correlation between rs763780 polymorphism and cancer susceptibility in Caucasian populations. This updated meta-analysis confirms that rs2275913 and rs763780 polymorphisms are highly associated with increased risk for multiple forms of cancer.

The IL-17A G-197A and IL-17F 7488T/C polymorphisms are associated with increased risk of cancer in Asians: a meta-analysis.

BackgroundInterleukin-17 (IL-17) is a family of emerged pro-inflammatory cytokines. The IL-17A and IL-17F are two important members of IL-17 family. Previous studies have shown that the functional IL-17A G-197A and IL-17F 7488T/C polymorphisms may contribute to susceptibility to cancer but the results were inconclusive. This meta-analysis was performed to determine the exact association between IL-17 polymorphisms and cancer risk.MethodsOnline databases were searched to identify eligible case–control studies. Pooled odds ratios (ORs) and confidence intervals (CIs) were calculated by fixed-effect models or random-effect models. Publication bias was detected by Egger’s test and Begg’s test.ResultsNine eligible case–control studies of IL-17A G-197A and seven studies of IL-17F 7488T/C, including 3,181 cases and 4,005 controls, were identified. Pooled analysis suggested the variant IL-17A-197A allele was associated with increased risk cancer (GA/AA vs GG, OR =1.27, 95% CI: 1.15, 1.41, Pheterogeneity =0.374; and A vs G, OR =1.30, 95% CI: 1.17, 1.45, Pheterogeneity =0.021). For IL-17F 7488T/C, the homozygote 7488CC genotype significantly increased risk of cancer (CC vs TC/TT, OR =1.36, 95% CI: 0.97, 1.91, Pheterogeneity =0.875; and CC vs TT, OR =1.39, 95% CI: 1.03, 1.88, Pheterogeneity =0.979), especially for gastric cancer.ConclusionThe variant IL-17A-197A allele and IL-17F 7488CC genotype were associated with increased risk of cancer, especially for gastric cancer.

The Influence of Polymorphisms of Interleukin-17A and -17F Genes on Susceptibility and Activity of Rheumatoid Arthritis.

The roles of interleukin (IL)-17A and IL-17F in the pathogenesis of rheumatoid arthritis (RA) have been previously studied. However, the relationships between polymorphisms (IL-17A G197A, the IL-17F 7488A/G, and the IL-17F 7383A/G) of these genes with RA have not been clarified yet. To investigate the impacts of these polymorphisms on the severity and susceptibility of RA in a Turkish population. One hundred sixty-one patients with RA and 88 healthy sex-, age-, and ethnicity-matched controls were enrolled in this study. The erythrocyte sedimentation rate, C-reactive protein (CRP), and disease activity scores 28 (DAS28) of all participants were recorded. The IL-17A G197A, the IL-17F 7488A/G, and 7383A/G polymorphisms were determined using the polymerase chain reaction-restriction fragment length polymorphism method. We found no significant difference regarding genotypes or allelic frequency distributions of the IL-17A G197A, the IL-17F 7383A/G, and 7488A/G polymorphisms between patients and healthy controls (p>0.05). There were slight, but not significant, differences in terms of CRP levels associated with the distribution of the genotypes of the IL-17F 7488A/G, and regarding DAS28 levels according to the genotype distribution of the IL-17A G197A polymorphism (p=0.062, 0.087, 0.052, respectively). These findings suggest that future larger scale studies with increased power should be performed to determine if the IL-17F 7488A/G and the IL-17A G197A polymorphisms are associated with the disease activity in patients with RA.

Involvement of IL17A, IL17F and IL23R Polymorphisms in Colorectal Cancer Therapy.

IL23/IL17 pathway plays an important role in the development of inflammatory bowel diseases (IBD). In general, the genes encoding the cytokines are genetically polymorphic and polymorphisms in genes IL23R and IL17 have been proved to be associated with its susceptibility to inflammatory diseases as well as cancer including colorectal cancer. Moreover, it has been shown that these interleukins are involved in anti-tumor or pro-tumor effects of various cancers. Previously, we showed that there is a significant association between IL17A, IL17F and IL23R polymorphisms as well as the occurrence of colorectal cancer and the clinical features of the disease. The purpose of the present work is to investigate an association between IL17A, IL17F and IL23R polymorphisms in 102 Tunisian patients with colorectal cancer treatment. The association was analyzed by statistical tools. We found that patients with mutated genotypes of IL17A G197A SNP could be a risk factor for the inefficiency of chemotherapy and radiotherapy. Unlike IL17F variant, patients with wild type genotypes require surgery and adjuvant chemotherapy. On the one hand, we found no evidence that supports a significant association between IL23R polymorphism and the combined genotypes of these three genes and the colorectal cancer treatment. On the other hand, we showed that there is an important interaction between IL17A/IL17F polymorphisms and the stage of the disease as well as its treatment. Finally, patients with IL17F wild type genotype highlighted that there is a valid longer OS without all treatments and with radiotherapy and a neoadjuvant chemotherapy. In contrast, we observed that there are no relationships between IL17A, IL23R and the survival of these patients neither with nor without the treatment. Our results suggest that polymorphisms in IL17A and IL17F genes may be a predictive source of colorectal cancer therapy type. Therefore, IL17F may serve as an independent prognostic factor for overall survival in patients with colorectal cancer.

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.

Significant association between interleukin-17A polymorphism and colorectal cancer

Interleukin (IL) 17A is an inflammatory cytokine expressed by Th 17 cells and plays a role in tissue inflammation by inducing release of proinflammatory and neutrophil-mobilizing cytokines. We have investigated the association between colorectal cancer and polymorphisms of IL17A (rs2275913. G197A). The study was performed in 241 subjects (102 with colorectal cancer and 139 healthy controls). Genotypes were determined by fluorescent-based restriction fragment length polymorphism method. The association between the molecular features at the gene in relation to tumor and patient clinical characteristics was analyzed. There was a significant difference between the genotype frequencies of IL17A G197A of control subjects (GG 68.34 % and GA + AA 31.65 %) and patients with colorectal cancer (GG 47.05 % and GA + AA 52.94 %) (p = 0.001 with odds ratio (OR) 2.45 (1.43-4.11)). IL17A G197A polymorphism is particularly associated with colon cancer. Indeed, the IL17A GG genotype could be considered as a protective factor against colon cancer (p = 0.00001) with OR 3.77 (2.04-6.99). We have noted a significant association of IL17A G197A polymorphism not only with tumor localization (p = 0.003) but also with tumor differentiation (p = 0.0005) in CRC patients. We have also showed a significant association of G197A variant with an increased risk of advanced stage (p = 0.005). Our result suggests that the A allele of IL17A gene is involved in susceptibility to colorectal cancer and is associated with clinical features as tumor location, tumor differentiation, and TNM stage. IL17A polymorphism may serve as biomarker of disease location and progression.

Association of IL-17A and IL-17F single nucleotide polymorphisms with susceptibility to osteoarthritis in a Korean population

The damage incurred in osteoarthritis (OA) is mediated by a variety of cytokines, growth factors and inflammatory mediators. The importance of the interleukin-17 (IL-17) family in inflammatory and autoimmune disease is becoming increasingly apparent. Microsatellite association mapping reveals a primary osteoarthritis susceptibility locus on chromosome 6p12.3-q13. IL-17A and IL-17F genes that resided on chromosome 6p12.3-q13 are believed to play an important role in the primary OA susceptibility. We investigated the allele and genotype of IL-17A G-197A and IL-17F T7488C in 302 OA patients and 300 healthy subjects as controls. We employed a PCR-SSCP assay to identify the genotypes IL-17A G-197A and IL-17F T7488C. For IL-17A G-197A, there were significant differences in frequencies of genotype and allele of IL-17A G-197A between OA patients and controls (both p<0.0001). For IL-17F T7488C, there were no significant differences in the allele frequency and genotype distribution for IL-17F T7488C between OA patients and controls (p=0.938 and p=0.1735, respectively). In conclusion, current study showed that polymorphism of IL-17A G-197A may be closely associated with susceptibility to the development of OA in the Korean population. However, there was no relationship between IL-17F T7488C polymorphism and OA susceptibility.

Association between Polymorphisms in Interleukin-17A and -17F Genes and Chronic Periodontal Disease

Objective. Interleukin-17 (IL-17) is a cytokine that induces neutrophil recruitment and the release of inflammatory mediators in several inflammatory conditions; nevertheless, the involvement of IL-17 gene polymorphisms in chronic periodontitis (CP) has not been addressed yet. Our aim was to evaluate the association between periodontal status and the polymorphisms IL-17A G197A and IL-17F C7488T in subjects with CP along with their impact on levels of inflammatory mediators. Material and Methods. Genomic DNA was obtained from 30 CP patients and 30 healthy controls (HCs). IL-17A G197A and IL-17F C7488T polymorphisms were determined using PCR-RFLP. Serum and periodontal tissues were collected and processed for ELISA, myeloperoxidase (MPO), and/or microscopic analysis. Results. The frequencies of genotypes in the CP group were significantly different from those of HC. Odds ratio indicated that increased risks for CP were associated with the -197A allele, not with the -7488T allele. In addition, the -197A allele was correlated with worse clinical parameters, higher MPO activity, and increased expression of inflammatory mediators (IL-17A and IL-8) than the other genotypes. Conclusions. These results indicate that the IL-17A -197A allele is associated with increased risk for CP, likely because this genotype relates to the enhanced inflammation in periodontal tissues.

Association between polymorphisms in interleukin‐17A and interleukin‐17F genes and risks of gastric cancer

Chronic inflammation is the hallmark of the pathogenesis of Helicobacter pylori-induced gastric cancer. Interleukin (IL)-17A and IL-17F are inflammatory cytokines expressed by a novel subset of CD4+ Th cells and play critical function in inflammation and probably in cancer. We conducted a case-control study including 1,010 gastric cancer patients and 800 healthy controls to assess the association between IL-17A G197A and IL-17F A7488G polymorphisms and risk of gastric cancer. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing. Logistic regression and Cox-proportional hazards analyses were used to evaluate the associations between polymorphisms and gastric cancer susceptibility, clinicopathological features and survival. After adjusted for age and gender, IL-17F 7488GA and GG genotypes were associated with an increased risk of gastric cancer compared with AA genotype [OR 1.51, 95% confidence interval (CI): 1.22-1.87 for GA; OR 1.61, 95% CI: 1.03-2.51 for GG]. Further stratification analyses indicated that the effect of IL-17F 7488GA genotype was noteworthy in gastric cancer patients of noncardia, intestinal type, poorly and moderately differentiated, age older than 40, large tumor size and lymph node metastasis. IL-17A 197AG genotype was associated with increased risk of poorly differentiated, TNM I/II, age of 40-65-year subtypes of gastric cancer, but not with total gastric cancer risk (p = 0.098). No significant relationship was observed between polymorphisms and survival of gastric cancer patients. These findings suggest that polymorphism of IL-17F 7488 involved in susceptibility to gastric cancer, which also influenced certain subtypes according to clinicopathological features, whereas IL-17A 197 may be less relevant.