IL-17A Rs2275913 Research Articles

Association between interleukin-17 gene polymorphisms and the risk of laryngeal cancer in a Chinese population.

IL-17 is associated with the occurrence and development of laryngeal cancer. However, no study has reported the association between IL-17 polymorphisms and laryngeal cancer susceptibility. Therefore, we analyzed the association of three polymorphism loci (rs2275913, 197 G/A; rs3748067, 383 A/G; and rs763780, 7488 T/C) of IL-17A and IL-17F with laryngeal cancer in the Chinese population. A case-control study was performed with 325 patients and 325 controls. Polymorphisms were detected by polymerase chain reaction and sequencing methods. SPSS17.0 software was used for statistical analysis. Allele and genotype frequencies of IL-17A rs2275913 were significantly different between patients and controls (P < 0.05). Frequencies of rs2275913 (197 G/A) AA and GA+AA genotypes compared to the GG genotype were significantly higher in patients than in controls, indicating the association of these genes with laryngeal cancer susceptibility; adjusted OR values were 2.54 (1.50-4.23) and 1.62 (1.19-2.17), respectively. Furthermore, individuals with the GA+AA genotype, compared to the GG genotype, aged ≤60 years, with smoking and alcohol consumption habits, and without a family history of cancer showed a higher cancer risk (OR = 2.74, 95%CI = 1.41-5.23; OR = 2.11, 95%CI = 1.21-3.55; OR = 1.91, 95%CI = 1.02-3.70; OR = 1.99, 95%CI = 1.08-3.39, respectively). In conclusion, the rs2275913 IL-17A (197 G/A) is associated with the incidence and development of laryngeal cancer in the Chinese population, and the AA and GA+AA genotypes harbor a high laryngeal cancer risk.

Genes associated with persistent lumbar radicular pain; a systematic review.

BackgroundThe aim of the present study was to provide an overview of the literature addressing the role of genetic factors and biomarkers predicting pain recovery in newly diagnosed lumbar radicular pain (LRP) patients.MethodsThe search was performed in Medline OVID, Embase, PsycInfo and Web of Science (2004 to 2015). Only prospective studies of patients with LRP addressing the role of genetic factors (genetic susceptibility) and pain biomarkers (proteins in serum) were included. Two independent reviewers extracted the data and assessed methodological quality.ResultsThe search identified 880 citations of which 15 fulfilled the inclusion criteria. Five genetic variants; i.e., OPRM1 rs1799971 G allele, COMT rs4680 G allele, MMP1 rs1799750 2G allele, IL1α rs1800587 T allele, IL1RN rs2234677 A allele, were associated with reduced recovery of LRP. Three biomarkers; i.e., TNFα, IL6 and IFNα, were associated with persistent LRP.ConclusionThe present results indicate that several genetic factors and biomarkers may predict slow recovery in LRP. Still, there is a need for replication of the findings. A stricter use of nomenclature is also highly necessary.Trial registrationThe review is registered PROSPERO 20th of November 2015. Registration number is CRD42015029125.

An Association Between Functional Polymorphisms of the Interleukin 1 Gene Complex and Schizophrenia Using Transmission Disequilibrium Test.

IL1 gene complex has been implicated in the etiology of schizophrenia. To assess whether IL1 gene complex is associated with susceptibility to schizophrenia in Polish population we conducted family-based study. Functional polymorphisms from IL1A (rs1800587, rs17561, rs11677416), IL1B (rs1143634, rs1143643, rs16944, rs4848306, rs1143623, rs1143633, rs1143627) and IL1RN (rs419598, rs315952, rs9005, rs4251961) genes were genotyped in 143 trio with schizophrenia. Statistical analysis was performed using transmission disequilibrium test. We have found a trend toward an association of rs1143627, rs16944, rs1143623 in IL1B gene with the risk of schizophrenia. Our results show a protective effect of allele T of rs4251961 in IL1RN against schizophrenia. We also performed haplotype analysis of IL1 gene complex and found a trend toward an association with schizophrenia of GAGG haplotype (rs1143627, rs16944, rs1143623, rs4848306) in IL1B gene, haplotypes: TG (rs315952, rs9005) and TT (rs4251961, rs419598) in IL1RN. Haplotype CT (rs4251961, rs419598) in IL1RN was found to be associated with schizophrenia. After correction for multiple testing associations did not reach significance level. Our results might support theory that polymorphisms of interleukin 1 complex genes (rs1143627, rs16944, rs1143623, rs4848306 in IL1B gene and rs4251961, rs419598, rs315952, rs9005 in IL1RN gene) are involved in the pathogenesis of schizophrenia, however, none of the results reach significance level after correction for multiple testing.

IL1A rs1800587 associates with chronic noncrisis pain in sickle cell disease.

Pain is prevalent in sickle cell disease (SCD) patients who display great heterogeneity in pain severity and frequency. Hypothesizing that inflammatory factors are involved in the pathogenesis of SCD pain, we focused on the IL1A C/T polymorphism rs1800587 that is an SNP located in a cis-transcriptional regulatory region. We genotyped IL1A rs1800587 and performed association studies with phenotype data obtained by a multidimensional pain assessment tool using the PAINReportIt® Questionnaire. Each T allele was associated with a 3.9 increase in composite pain index score (p = 0.04) as determined by multiple linear regression. IL1A rs1800587 may influence chronic pain in SCD.

IL12 Gene Polymorphism in Association with Hepatocellular Carcinoma in HCV-infected Egyptian Patients

ABSTRACTBackground: Hepatocellular carcinoma has been recorded the commonest cancer in Egypt. This increasing incidence may be attributed to the high prevalence of hepatitis C virus with its complications, so this study aimed to investigate the association between the potentially functional polymorphisms of IL12A and IL12B genes as a risk factor of development of hepatocellular carcinoma (HCC) on top of hepatitis C virus (HCV) infection in an Egyptian population.Materials and methods: We genotyped two loci of IL12 which were rs568408 (3’UTR G>A) for IL12A and rs3212227 (3’UTR A>C) for IL12B in 78 patients with HCC on top of chronic HCV infection. In addition, 64 cancer-free chronic HCV patients were studied, besides 92 healthy subjects who were included as control.Results: Study of rs568408 (G>A) gene polymorphism showed that the A allele is higher while the G allele is lower in HCC cases than cancer-free chronic HCV patients (p = 0.006*). The A-containing genotypes AG and (AG+AA) were higher while the GG was lower (p = 0.009* and p = 0.005*), respectively. The study of the rs3212227 (A>C) polymorphism showed neither statistically significant differences between the C and A allele (p = 0.2) nor between CC, AC, or AC+CC in HCC cases and cancer-free chronic HCV patients (p = 0.7, p = 0.2, and p = 0.29), respectively.Conclusion: Our findings showed that IL12A rs568408 (G>A) polymorphism may contribute to the risk of HCC on top of chronic HCV infection, whereas that of IL12B rs3212227 (A>C) do not.

Association Between IL12A rs568408, IL12B rs3212227 and IL-12 Receptor rs383483 Polymorphisms and Risk of Pulmonary Tuberculosis

Background: Interleukine-12 (IL-12) induced interferon- (IFN- ) production and development of T cells into Th1 cells, which has a critical role in immunity to intracellular pathogens. Objectives: The current study aimed to evaluate the possible association between IL12A rs568408, IL12B rs3212227 as well as IL-12 receptor (IL-12R) rs383483 polymorphisms and pulmonary tuberculosis (PTB). Methods: This case-control study was conducted on 174 confirmed PTB patients and 177 healthy subjects in a sample of southeast Iranian population. Genotyping was performed by the tetra amplification refractory mutation system- polymerase chain reaction (T-ARMS-PCR) method. Results: The frequencies of GG, GA and AA genotypes of IL12A rs568408 variant in cases and controls were 58.9%, 38.5%, 1.7% and 61.6%, 37.3%, 1.1%, respectively. Regarding rs3212227 variant, the frequencies of AA, AC and CC genotypes in cases and controls were 47.1%, 54.4%, 7.5% and 50.8%, 43.5%, 5.7%, respectively. Concerning IL12R rs383483 polymorphism, the frequencies of AA, AG and GG in cases and controls were 39.1%, 31.4%, 29.5% and 40.2%, 25.3%, 34.5%, respectively. There was no significant difference in allele and genotype frequency of IL12A rs568408, IL12B rs3212227 and IL-12R rs383483 polymorphisms between patients with PTB and control groups (P > 0.05). Conclusions: The findings of the current study show that neither IL12A rs568408 and IL12B rs3212227 nor IL-12R rs383483 polymorphisms are associated with the risk of PTB in our population. Further studies with larger sample sizes and various ethnicities are needed to certify our findings.

Association of IL-17A/F polymorphisms with the risk of gastritis and gastric cancer in the Korean population

We investigated the effects of IL-17A rs2275913 and IL-17F rs763780 polymorphisms on IL-17 expression and the association of these polymorphisms with the risk of gastritis and gastric cancer. IL-17A expression was closely associated with the degree of gastritis in 55 non-neoplastic gastric mucosae and was markedly decreased in subjects carrying A allele. In addition, IL-17F expression was increased in the T allele carriers, but was not associated with gastritis. In 300 gastric cancer patients, the frequency of the rs2275913 A/A genotype was significantly higher in intestinal-type gastric cancer, when compared to that of diffuse-type gastric cancer (P>0.05). There was a significant difference in genotype distribution and allele frequencies of IL-17F rs763780 when comparing gastric cancer patients and 247 healthy controls. These results suggest that the polymorphisms of IL-17F rs763780 and IL-17A rs2275913 are closely associated with susceptibility to the development of gastritis and gastric cancer in the Korean population.

Asthma and rhinitis have different genetic profiles for IL13, IL17A and GSTP1 polymorphisms

BackgroundAsthma and rhinitis have a complex etiology, depending on multiple genetic and environmental risk factors. An increasing number of susceptibility genes are currently being identified, but the majority of reported associations have not been consistently replicated across populations of different genetic backgrounds. PurposeTo evaluate whether polymorphisms of IL4R (rs1805015), IL13 (rs20541), IL17A (rs2275913) and GSTP1 (rs1695) genes are associated with rhinitis and/or asthma in adults of Portuguese ancestry. Methods192 unrelated healthy individuals and 232 patients, 83 with rhinitis and 149 with asthma, were studied. All polymorphisms were detected by real time polymerase chain reaction (PCR) using TaqMan assays. ResultsComparing to controls, significant association with asthma was observed for GSTP1 rs1695 AA genotype (odds ratio (OR) – 1.96; 95% CI – 1.18 to 3.25; p=0.010). The association sustains for allergic asthma (OR – 2.17; 95% CI – 1.23 to 3.80; p=0.007). IL13 rs20541 GG genotype was associated with less susceptibility to asthma (OR – 0.55, 95% CI – 0.33 to 0.94, p=0.028). Among patients, IL17A rs2275913 AA genotype was less associated with asthma than with rhinitis (OR – 0.20; 95% CI of 0.07 to 0.56; p=0.002). A similar association was found for IL13 rs20541 GG genotype (OR – 0.48; 95% CI of 0.25 to 0.93; p=0.031). There were no significant differences in the distribution of allelic and genotypic frequencies between patients and controls for the IL4R polymorphism’ analyzed. ConclusionThese results support the existence of a significant association between GSTP1 rs1695 and IL13 rs20541 SNPs, with susceptibility to asthma, in the population studied. Different genotype profiles of IL17A and IL13 genes seem to influence the clinical pattern of disease expression mainly confined to the upper airways, as rhinitis, or including the lower airways, as asthma.

Precision assessment of heterogeneity of lymphedema phenotype, genotypes and risk prediction

Lymphedema following breast cancer surgery is considered to be mainly due to the mechanical injury from surgery. Recent research identified that inflammation-infection and obesity may be the important predictors for lymphedema. The purpose of this exploratory research was to prospectively examine phenotype of arm lymphedema defined by limb volume and lymphedema symptoms in relation to inflammatory genes in women treated for breast cancer. A prospective, descriptive and repeated-measure design using candidate gene association method was used to enroll 140 women at pre-surgery and followed at 4–8 weeks and 12 months post-surgery. Arm lymphedema was determined by a perometer measurement of ≥5% limb volume increase from baseline of pre-surgery. Lymphedema symptom phenotype was evaluated using a reliable and valid instrument. Saliva samples were collected for DNA extraction. Genes known for inflammation were evaluated, including lymphatic specific growth factors (VEGF-C & VEGF-D), cytokines (IL1-a, IL-4, IL6, IL8, IL10, & IL13), and tumor necrosis factor-a (TNF-a). No significant associations were found between arm lymphedema phenotype and any inflammatory genetic variations. IL1-a rs17561 was marginally associated with symptom count phenotype of ≥8 symptoms. IL-4 rs2070874 was significantly associated with phenotype of impaired limb mobility and fluid accumulation. Phenotype of fluid accumulation was significantly associated with IL6 rs1800795, IL4 rs2243250 and IL4 rs2070874. Phenotype of discomfort was significantly associated with VEGF-C rs3775203 and IL13 rs1800925. Precision assessment of heterogeneity of lymphedema phenotype and understanding the biological mechanism of each phenotype through the exploration of inherited genetic susceptibility is essential for finding a cure. Further exploration of investigative intervention in the context of genotype and gene expressions would advance our understanding of heterogeneity of lymphedema phenotype.

Common variants in IL-17A/IL-17RA axis contribute to predisposition to and progression of congestive heart failure.

Heart failure is characterized by immune activation leading to production and release of proinflammatory cytokines. Interleukin 17A (IL-17A) is a proinflammatory cytokine and multiple lines of evidence from animal and human studies suggest crucial roles of IL-17A in heart failure. Therefore, we investigated whether common polymorphisms of genes IL17A and IL17RA (coding interleukin 17 receptor A) contribute to genetic predisposition to heart failure and adverse clinical outcomes associated with it.A total of 1713 adult patients with congestive heart failure and 1713 age- and sex-matched controls were genotyped for promoter single nucleotide polymorphisms (SNPs), rs2275913 and rs8193037 in IL17A and rs4819554 in IL17RA, to assess the relationship between individual SNPs and the risk of congestive heart failure. Results showed that rs8193037 in IL17A was associated with the risk of congestive heart failure (odds ratio [OR] = 0.76; 95% confidence interval [CI] 0.63-0.90, adjusted P = 0.002) after adjustment for multiple cardiovascular risk factors including age, sex, smoking status, diabetes, hypertension, and dyslipidemia. This association was evident in both ischemic and nonischemic heart failure (P = 0.005 and P = 0.05, respectively). Furthermore, prospective follow-up of 12.7 months for the occurrence of adverse clinical outcomes showed that rs4819554 in IL17RA was significantly associated with cardiovascular mortality (hazard ratio [HR] = 1.28; 95% CI = 1.02-1.59, adjusted P = 0.03) after adjustments for multiple cardiovascular risk factors and New York Heart Association functional class.This study demonstrated associations of rs8193037 in the promoter of IL17A with the risk of congestive heart failure, and of rs4819554 in the promoter of IL17RA with the risk of cardiovascular mortality in patients with congestive heart failure. These data lend further support to the notion that immune activation and genetic polymorphisms contribute to heart failure pathogenesis and progression.

Meta-Analysis for the Association between Polymorphisms in Interleukin-17A and Risk of Coronary Artery Disease.

Coronary artery disease (CAD) is a disease which has become a leading cause of death worldwide. The polymorphisms in Interleukin-17 (IL-17A), including rs2275913, rs3819024, rs3819025, rs3748067, rs8193037, rs4711998, and rs8193036, have been found to be probably associated with the risk of CAD. However, the results were inconsistent and inconclusive. The present study performed a meta-analysis to get a more precise and comprehensive estimation of the association between the IL-17A polymorphisms and CAD risk. The Pubmed, Embase, Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure, and Chinese Biomedical Literature Databases were searched for related studies. A total of six studies, including 3542 cases and 3212 controls, were identified for the meta-analysis. The main findings of the present meta-analysis show that the TT genotype of IL-17A rs3748067 is associated with a significant lower risk of CAD in the homozygous model odds ratio (OR) (OR = 0.37) in Asians. No significant association was found for rs2275913, rs3819024, rs3819025, rs8193037, rs4711998, and rs8193036 with CAD susceptibility in the overall analysis. However, subgroup analysis indicated a significant decreased risk of CAD for the GG genotype and G allele of rs2275913 in a small sample size group, and a higher risk of CAD for the GG genotype and G allele of rs8193037 in a heterozygous model (OR = 1.56), dominant model (OR = 1.54), and allelic model (OR = 1.47) in Asians. In conclusion, the current meta-analysis suggests a significant relationship between rs3748067, rs8193037, and CAD in Asians, while for rs2275913, rs3819024, rs3819025, rs4711998, rs8193036, no such relations were found. Thus, IL-17A rs3748067 and rs8193037 might be recommended as a predictor for susceptibility of CAD for Asians. However, the results of this meta-analysis are hypothesis-generating results which should be interpreted with caution because of the heterogeneity and publication bias among study designs.

Polymorphism of IL-10 gene promoter region: association with T cell proliferative responses after acellular pertussis vaccination in adults.

Individual variation in immune responses is always encountered after vaccination. This phenomenon is also seen after acellular pertussis vaccination. The aim of this present study was to investigate whether single nucleotide polymorphisms (SNPs) in the IL-10 gene promoter region (rs1800890, rs1800896, rs1800871), IL-12B (rs2546890), IL-12RB1 (rs372889), IL-17A (rs2275913), and IL-23R (rs11209026) affect the immune responses after acellular pertussis vaccination. The T cell proliferative response was evaluated in 38 Finnish young adults who received a second booster dose of a vaccine combination of diphtheria, tetanus, and acellular pertussis, 10years after the previous booster. The response was evaluated with a proliferation assay in which vaccine antigens pertussis toxin (PT), filamentous hemagglutinin (FHA), and pertactin (PRN) were used for the stimulation, before and 1month after the second vaccination. Specific proliferation of peripheral blood mononuclear cells against pertussis antigens was affected by IL-10 SNP in the promoter region at position -1082 (A>G, rs1800896). One month after the vaccination, subjects with the AA and AG genotypes had a significantly higher T cell proliferative response against PT and FHA compared to those with the GG genotype. Subjects with the GG genotype had the lowest responses. As a conclusion, our preliminary results indicate that IL-10 SNP -1082 might play an important role in T cell-mediated immune responses after acellular pertussis vaccination.

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.

A functional variant at miRNA-122 binding site in IL-1a 3' UTR predicts risk of recurrence in patients with oropharyngeal cancer.

IL-1α, an important regulator of immune and inflammation responses, has been implicated in cancer development and prognosis. An insertion (Ins)/deletion (Del) polymorphism (IL-1α rs3783553) in the 3′ UTR of IL-1α may disrupt a binding site for miRNA-122 and may affect its transcription level. Thus, this polymorphism may cause interindividual variation in immune and inflammation responses and thus may lead to different susceptibility to treatment response and prognosis of such patients. We evaluated the association of IL-1α rs3783553 polymorphism with risk of recurrence of squamous cell carcinoma of the oropharynx (SCCOP) in a cohort of 1008 patients. Log-rank test and univariate and multivariable Cox models were used to evaluate associations. Compared with patients with Del/Del homozygous genotype, the patients with Ins/Del+Ins/Ins variant genotypes had worse disease-free survival (log-rank P < 0.0001) and increased risk of SCCOP recurrence (HR, 2.4, 95% CI, 1.7-3.3) after multivariable adjustment. Furthermore, among patients with HPV16-positive tumors, the patients with Ins/Del+Ins/Ins variant genotypes of the IL-1α polymorphism had worse disease-free survival (log-rank P < 0.0001) and much higher recurrence risk than those with Del/Del homozygous genotype of this polymorphism (HR, 16.3, 95% CI, 5.0-52.7). Our findings suggest that IL-1α rs3783553 polymorphism may modulate the risk of SCCOP recurrence in patients, particularly for patients with HPV16-positive tumors. However, larger studies are needed to validate these results.

INTERLEUKIN 1A GENE POLYMORPHISMS IN ROMANIAN PATIENTS WITH SERONEGATIVE SPONDYLOARTHROPATHIES

Objective. The aim of this study was to investigate whether two IL1A gene polymorphisms, rs17561 and rs1800587, influence disease susceptibility for seronegative spondyloarthropathies (SpA) in Romanians. Subsequently, we analysed separately ankylosing spondylitis (AS) and psoriatic arthritis (PsA) subgroups in relation with the two IL1A gene variants. Methods. The study included 240 SpA patients (140 AS and 100 PsA patients) and 160 healthy controls. Real-time polymerase chain reaction (RT-PCR) was used to genotype the two single nucleotide polymorphisms (SNPs). Allele, genotype and haplotype frequencies of each SNP were compared between SpA patients and controls and also between AS and PsA cohorts and controls. The PLINK 1.9 software package was used to assess the potential associations; p values ≤ 0.05 were considered significant. Results. The minor allele T frequency for rs17561 polymorphism was similar in general SpA cohort (31.4%) compared with controls (32.8%), the statistical analyses confirming the lack of association (p=0.67). Almost identical results were found for rs1800587: minor allele T frequency was 29.1% in SpA patients and 29.7% in controls (p=0.85). The same pattern persisted for the separate analysis of HLA-B27 positive SpA patients or AS and PsA cases against controls. Conclusions. The IL1A gene polymorphisms (rs17561 and rs1800587) do not influence the disease predisposition for seronegative spondyloarthropathies in general, nor for ankylosing spondylitis and psoriatic arthritis in particular, in Romanians.

An insertion/deletion polymorphism in the interleukin-1A 3'untranslated region confers risk for gastric cancer.

The aim of the study was to evaluate whether the insertion/deletion polymorphism (rs3783553) locating in the 3' untranslated region (3'UTRs) of IL-1A was related to the risk of gastric cancer (GC) in a Chinese population and explore the possible molecular mechanism. Genomic DNA was extracted from peripheral venous blood of 519 GC patients and 536 healthy control individuals. The IL-1A rs3783553 polymorphism was genotyped by using a polymerase chain reaction assay. The vectors containing the insertion or deletion allele were constructed, and luciferase assay was used to detect the effect of the polymorphism on the transcriptional activity of IL-1A. Strong evidence of association was observed between the IL-1A rs3783553 polymorphism and susceptibility to GC in the study. In addition, the `TTCA' insertion allele of rs3783553 disrupts the binding site for miR-122 and miR-378, thereby increasing transcription of IL-1α in vitro. These findings suggest that functional polymorphism rs3783553 in IL-1A could contribute to GC susceptibility, possibly or at least partially through affecting the transcriptional activity of IL-1A.

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.

(280) Interleukin 1alpha rs1800587 associates with chronic non-crisis pain in sickle cell disease

Pain is prevalent in sickle cell disease (SCD) patients who display great heterogeneity in pain severity and frequency. Studying the contribution of relevant candidate gene polymorphisms may shed light on the etiology of the pain heterogeneity, allowing for precision pain medicine in SCD. We hypothesize that inflammatory factors are involved in the pathogenesis of sickle cell pain. In this study, we focused on the IL1A C/T polymorphism rs1800587 that is a single nucleotide polymorphism (SNP) located at position -889. The SNP came to our attention because our bioinformatic analysis predicted that this SNP is located in a cis-transcriptional regulatory region modulating the protein expression level. Pain phenotype data were gathered from PAINReportIt, a pain assessment tool for multidimensional pain experience. The composite pain index (CPI) was used as a measurement for the baseline pain. Utilization of urgent or emergency care due to sickling pain crisis was used as a surrogate for acute pain crisis in SCD. We found the T allele was associated with increased CPI. In our SCD cohort, each T allele was associated with a 3.9 increase in CPI (p=0.04), accounting for 3% of variability in CPI as determined by the additive multiple linear regression. We did not find significant association between this SNP and the patient utilization due to acute pain. These results represent the first indication that IL1A rs1800587 may influence the chronic non-crisis pain in SCD. This study was supported in part by grants from NIH (R01 HL124945, R01 HL098141 and T32DE018381).

Association Analysis of Interleukin-17 Gene Polymorphisms with the Risk Susceptibility to Tuberculosis.

Recently, many institutions have investigated the associations of interleukin-17 (IL17) polymorphisms with tuberculosis (TB) susceptibility, while those results are inconsistent. The purpose of this meta-analysis is to comprehensively assess whether IL17A rs22275913, IL17F rs763780, and IL17A rs3748067 polymorphisms are correlated with TB risk. Electronic bibliographic databases were searched for case-control studies which potentially focused on the relationship between the aforementioned polymorphisms and TB risk on October 15th, 2015. Pooled odds ratios (OR) combined with 95% confidence intervals (CI) were employed to assess the associations. There was no significant association of IL-17A rs22275913 polymorphism with susceptibility to TB in Asians or Caucasians. For IL-17A rs3748067 polymorphism, significant associations were observed in Asian (T vs. C: OR 1.461, 95% CI 1.158-1.844, P=0.001; TT vs. CC: OR 1.871, 95% CI 1.140-3.069, P=0.013; TT/TC vs. CC: OR 1.392 95% CI 1.062-1.825, P=0.017; TT vs. OR 1.820, 95% CI 1.111-2.981, P=0.017). For IL-17F rs763780, we detected the significant associations under allele contrast, heterozygote, dominant and recessive models (C vs. T: OR 1.571, 95% CI 1.352-1.824, P=0.000; CT vs. TT: OR 1.624, 95% CI 1.346-1.958, P=0.000; CT/TT vs. TT: OR 1.639, 95% CI 1.381-1.946, P=0.000, respectively). The corresponding results were also detected in Asian populations (C vs. T: OR 1.068, 95% CI 1.380-1.875, P=0.000; CT vs. TT: OR 1.689, 95% CI 1.390-2.053, P=0.000; CT/TT vs. TT: OR 1.695, 95% CI 1.420-2.023, P=0.000), while there were no significant associations in Caucasian. IL-17F rs763780 allele C and IL-17A rs3748067 allele C may be involved in the susceptibility to TB in Asian populations. There were no significant associations between IL-17A rs22275913 polymorphism and risk of TB.

Genetic Analysis of IL-17 Gene Polymorphisms in Gout in a Male Chinese Han Population.

Interleukin (IL)-17 is a proinflammatory cytokine mainly secreted by activated T helper 17 cells and involved in inflammatory immune responses. This study aimed to investigate the association between IL-17 variants as well as serum IL-17 levels with gout in male Chinese Han individuals. A total of 1,101 male gout patients and 1,239 ethic-matched controls were enrolled. Genetic distributions of three variants (rs2275913 in IL-17A, rs763780 in IL-17F, and rs4819554 in IL-17RA) were detected by real-time polymerase chain reaction using the Taqman probe method. The plasma concentrations of IL-17A and IL-17F were measured in 228 gout patients and 198 controls that came from above samples by an enzyme-linked immunosorbent assay. No significant differences were observed in the genetic distribution of these polymorphisms between cases and controls (rs2275913: χ2 = 0.15, p = 0.928 by genotype, χ2 = 0.14, p = 0.711 by allele; rs763780: χ2 = 2.24, p = 0.326 by genotype, χ2 = 0.26, p = 0.609 by allele; rs4819554: χ2 = 1.79, p = 0.409 by genotype, χ2 = 1.46, p = 0.227 by allele). Levels of serum IL-17A and IL-17F were significantly decreased in gout patients (both p<0.001). However, no difference was observed in acute gout patients between different genotypic carriers of rs2275913 and rs763780 regarding serum IL-17A and IL-17F levels (p>0.05). Although the genetic variants in IL-17 we studied in this research do not appear to be involved in the development of gout in male Chinese Han individuals, the IL-17 cytokine family may participate in gouty inflammation in an undefined way, which requires further validation.