IL-10 Polymorphisms Research Articles

Association of single nucleotide polymorphisms in TNFA and CCR5 genes with Japanese Encephalitis: A study from an endemic region of North India

TNFA, IL1B, HMGB1, IL10, CXCL8, CCL2 and CCR5 gene polymorphisms were investigated in 183 Japanese Encephalitis (JE) cases and 361 healthy controls from North India. Higher frequency of TNFA rs1800629 G/A, CCR5 rs1799987 genotypes with A allele and lower frequency of combination lacking TNFA rs1800629 A, CCR5 rs333 Δ32, andCCR5 rs1799987 A alleles and CCL2 rs1024611 G/G genotype was observed in JE cases. TNFA rs1800629 A and CCR5 rs1799987 A alleles were associated with susceptibility while combination lacking TNFA rs1800629 A, CCR5 rs333 Δ32, and rs1799987 A alleles and CCL2 rs1024611 G/G genotype was associated with protection to JE.

Functional dyspepsia susceptibility is associated with TGFB1 gene polymorphisms (RS4803455, RS1800469) in Hpylori-negative Chinese population.

We previously published that altered expression of gastric TRPV1, BDNF, and peripheral cytokines was present in patients with functional dyspepsia. We herein examine whether genetic predisposition in altered biomarkers influences dyspeptic, sleep, and mood symptoms in patients with FD without previous infection. Consecutive adult FD patients (Rome III) with no recent history of gastroenteritis and asymptomatic age- and sex-matched healthy controls were recruited for upper endoscopy. Subjects with GERD and IBS as predominant symptoms, diabetes mellitus, current or previous Hpylori infection, psychiatric illness, and recent use of NSAID or PPI were excluded. The genetic associations with dyspeptic symptoms, sleep quality, and mood symptoms were evaluated. Genetic polymorphisms in TRPV1, TGFB1, TNF, COMT, BDNF, IL6, IL8, IL10, and IL12 were analyzed. Twenty-nine male FD patients and 104 female FD patients were age matched (±3years) with 81 healthy subjects. All had postprandial distress syndrome (PDS) as predominant subtype (PDS: 130, EPS: 3). SNPs in TGFB1 showed significant associations in dyspeptic patients after age and sex adjustment [for RS4803455: in the codominant model (C/A, OR=0.34 (0.18-0.65), P=.004); in the dominant model (genotype C/C vs C/A-A/A, OR=0.42 (0.23-0.77), P=.004); and in the overdominant model (genotype C/C-A/A vs C/A, OR=0.38 (0.21-0.70), P<.001)] [for RS1800469: in dominant model (genotype A/A vs A/G-G/G, OR=0.52 (0.27-0.99), P=.043)]. A allele in RS4803455 was associated with higher HADS depression score (P=.05) and epigastric burning sensation(P=.01). Our data showed that dyspeptic patients predispose genetic difference in TGFB1 which may influence the severity of dyspepsia.

Year-Long Rhinovirus Infection is Influenced by Atmospheric Conditions, Outdoor Air Virus Presence, and Immune System-Related Genetic Polymorphisms.

Rhinovirus is a common picornavirus with over 150 serotypes and three species, which is responsible for half of the human common cold cases. In people with chronic respiratory conditions and elders, it may also cause life-threatening diseases. Transmission routes are not definitively established but may involve direct human-to-human and indirect transmission (surfaces and aerosols based). In the present study, year-long presence of virus was tested by qPCR in the nostrils of young healthy volunteers and indoor and outdoor air samples. Results were correlated to atmospheric conditions (meteorological and air quality parameters) and voluntaries immune system-related genetic polymorphisms (TOLLIP rs5743899, IL6 rs1800795, IL1B rs16944, TNFA rs1800629) typed by PCR-RFLP. Nasal samples showed increased frequency and viral titers of Rhinovirus in spring and autumn. No indoor air samples tested positive for Rhinovirus, whereas outdoor air samples tested positive in late autumn. Sun radiation, atmospheric SO2, and benzene levels correlated with nostrils Rhinovirus detection. Both IL6 and TOLLIP polymorphisms but not TNFA or IL1B influenced Rhinovirus detection in the nostrils of voluntaries. Taken together, the results indicate that Rhinovirus circulation is determined by environmental conditions (weather, air-borne virus, and air pollution) and genetically encoded individual variation in immunity.

STAT3 polymorphisms and IL-6 polymorphism are associated with the risk of basal cell carcinoma in patients from northern Poland

Basal cell carcinoma (BCC) environment consists of stromal and inflammatory cells which produce variety of cytokines, chemokines and growth factors that may affect tumor behavior. One of the cytokines suggested to be involved in the pathogenesis of BCC is IL-6, which is the upstream element of IL-6/JAK/STAT3 pathway. The correlation between polymorphisms of the genes related to this pathway and cancer risk/prognosis have been previously investigated in several neoplasia, but available data concerning BCC are scarce. In the present study, rs1800795 (-174 G/C) IL-6 gene polymorphism and two polymorphisms in the STAT3 gene, namely rs2293152 (intron 11, C/G) and rs4796793 (-1697, C/G) were assessed in relation to the BCC risk and clinical course. Additionally, IL-6 serum level was assessed in relation to IL-6 genotype and clinical variables. The study included 254 unrelated patients with BCC and of mean age 70.39 ± 11.43 (69.83 ± 12.32 women, 71.03 ± 10.31 men) and 198 healthy, unrelated age- and sex-matched volunteers. IL-6 and STAT3 polymorphisms were analyzed using polymerase chain reaction with sequence-specific primers (SSP-PCR). Serum concentration of IL-6 was measured using the ELISA test. We have found that the presence of C allele in rs1800795 IL-6 gene polymorphism was associated with increased risk of BCC (aOR 1.86; 95% CI 1.22–2.84; p = 0.004). The presence of CC genotype in STAT3 rs2293152 polymorphism was associated with increased BCC risk in recessive model analysis (aOR 3.94; 95% CI 1.59–9.77; p = 0.003). In contrast, the presence of GC genotype in overdominant model was associated with decreased risk of BCC (aOR = 0.24; 95% CI 0.12–0.49; p < 0.0001). The presence of C allele in STAT3 rs2293152 polymorphism was associated with increased risk of BCC (aOR 1.31; 95% CI 1.01–1.69; p = 0.04). The presence of GG genotype in STAT3 rs4796793 polymorphism was associated with increased BCC risk in recessive model analysis (aOR 3.66; 95% CI 1.33–10.10; p = 0.012). The presence of G allele in STAT3 rs4796793 polymorphism was associated with increased risk of BCC (aOR 1.59; 95% CI 1.01–2.49; p = 0.04). IL-6 serum level positively correlated with the tumor size.

Interleukin-6 gene polymorphism (-174 G/C) association with seropositive Toxoplasma gondii infection patients in Al-Diwaniyah hospital

The present study aims to detection Interleukin-6 gene polymorphism (-174 G/C) from seropositive Toxoplasma gondii pregnant women patients and healthy control from individuals reviewers to AL-Diwaniyah hospital. 80 samples were collected for the period from October 2018- April 2019, including two groups of 30 samples healthy control and 50 samples from pregnant women infected with Toxoplasma gondii. The results of the present study indicated the presence of IL-6 (-174 G/C) polymorphism in pregnant women infected with Toxoplasma gondii and healthy control. Where was observed that CG genotype more frequent in patients indicating the association of this genotype with the disease compared to the control group where CG genotype appears less. Also, the results of the current study indicate the appearance of allele C more frequently in pregnant women patients compared to healthy control. We can conclude from the present study there association of appearance allele C with Toxoplasma gondii infection.

The association between interleukin-1 polymorphisms and their protein expression in Chinese Han patients with breast cancer.

BackgroundBreast cancer (BC) is the most common cancer in women and the second leading cause of cancer‐related deaths among women worldwide. Single nucleotide polymorphisms (SNPs) in cytokine genes have been shown to alter their expressions or functions in patients with BC. In recent years, the molecular structure and function of IL‐1 have been studied. Its genetic polymorphism could affect the transcription and expression of the IL‐1 gene. Moreover, it is closely related to several diseases. This fact and plethora of gene polymorphism data prompted us to investigate the relationship between IL‐1 polymorphisms and IL‐1 protein expression in Chinese Han BC patients.MethodIn total, 298 patients with BC and 287 healthy control women were studied. The genetic polymorphisms for IL‐1 were analyzed by the MassARRAY sequencing method. Tumor markers and IL‐1β levels were measured by electrochemiluminescence and ELISA, respectively. All gene selection GRCh38 version.ResultsThe rs1143623 (NC_000002.12:g.112838252C>G) (GC), rs16944 (NC_000002.12:g.112837290A>G)(AG), and rs10490571 (NC_000002.12:g.102100877C>T) (CC) SNPs were found to be significantly lower in the BC group than in the controls. The variant G/C genotype of rs1143623 was associated with a significantly increased risk for BC (OR = 2.34, p < 0.05). The alleles for rs16944 (A/G; OR = 3.15, p < 0.05) and rs10490571 (T/C; OR = 2.48, p < 0.05) were also significantly associated with BC. Moreover, the genotypes of rs1143623, rs16944, and rs10490571 were significantly correlated with serum IL‐1β levels and other tumor markers.ConclusionOur data reveal the association between genetic polymorphisms of IL‐1 and BC susceptibility in the Chinese Han population and indicates that IL‐1 polymorphisms are closely associated with tumor markers and IL‐1β protein expression in BC patients.

IL-18 polymorphisms (-137C/G and -607A/C) are not associated with tuberculosis

Many studies have demonstrated that (IL-18) polymorphisms (including -137C/G and -607A/C) are correlated with the risk of tuberculosis. However, the meaning of this finding remains a matter of debate. In this study, electronic databases, including PubMed, EMBASE, Web of Science, Google Scholar and CNKI, were systemically queried to identify relevant studies. Subsequently, odds ratios and corresponding 95% confidence intervals were analysed. Our data indicated that the IL-18 -137C/G polymorphism was not related to tuberculosis susceptibility (GG vs. AA odds ratio = 0.71, 95% confidence interval 0.43–1.17; GA vs. AA: odds ratio =0.80, 95% confidence interval 0.57–1.13; dominant model: odds ratio = 0.78, 95% confidence interval 0.56–1.08; recessive model: odds ratio = 0.76, 95% confidence interval 0.46–1.25). Similarly, there was no association between the IL-18 -607A/C polymorphism and tuberculosis susceptibility (AA vs. CC: odds ratio = 1.25, 95% confidence interval 0.87–1.79; CA vs. CC: odds ratio = 1.10, 95% confidence interval 0.93–1.29; dominant model: odds ratio = 1.13, 95% confidence interval 0.90–1.41; recessive model: odds ratios=1.17, 95% confidence interval 0.90–1.53). No association was found in the subgroup analysis based on the Hardy–Weinberg equilibrium. In addition, there was no publication bias. The two IL-18 gene polymorphisms (-137C/G and -607A/C) were not markedly correlated with tuberculosis susceptibility. Well-designed studies with more subjects will be required for further validation of these results.

Association study of single nucleotide polymorphisms in IL-10 and IL-17 genes with the severity of microbial keratitis

PurposeExploratory analysis to assess the association of single nucleotide polymorphisms (SNPs) in the interleukin (IL) 10 and IL-17 genes with severity of contact lens keratitis. MethodsThis was a retrospective case control study of 88 contact lens keratitis cases (25 severe) and 185 healthy contact lens wearers recruited from studies conducted at Moorfields Eye Hospital and in Australia-wide during 2003–2005. Buccal swab samples were collected on Whatman FTA cards and mailed by post for DNA extraction and SNP genotyping. IL-10 (rs1800871; rs1800896; rs1800872) and IL-17 (rs1800871; rs1800896; rs1800872) SNPs were screened by pyrosequencing. Genetic association analyses were performed via Cochran-Armitage trend tests and logistic regression models using PLINK software. ResultsNone of the SNPs tested showed evidence of association with severity of contact lens keratitis at P < 0.05. Nevertheless, minor allele G in SNP rs2397084 of the IL-17F gene was associated with increased risk of severe MK, with OR=2.1 (95% CI=0.9-4.8, P = 0.066). ConclusionOur study cannot exclude with confidence that genetic variation in the IL-17 F proinflammatory cytokine is associated with more severe outcomes of MK. However, there is general body of information that the IL-17 pathway is important in the mechanisms of MK. Studies with larger power and the expanded array of laboratory tools will elucidate the exact role of IL-17 in MK.

Long- and short-term association of low-grade systemic inflammation with cardiovascular mortality in the LURIC study

The present study aimed to evaluate biomarkers representing low-grade systemic inflammation and their association with cardiovascular mortality in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. The included 3134 consecutive patients underwent coronary angiography between June 1997 and May 2001 with a median follow-up of 9.9years. Plasma levels of IL-6, and acute-phase reactants serum amyloid A (SAA) and C-reactive protein (CRP) were measured. SAA and IL-6 polymorphisms were genotyped. During a median observation time of 9.9years, 949 deaths (30.3%) occurred, of these 597 (19.2%) died from cardiovascular causes. High plasma levels of IL-6, CRP and SAA were associated with unstable CAD, as well as established risk factors including type 2 diabetes mellitus, smoking, low glomerular filtration rate, low TGs and low HDL-C. After adjusting for established cardiovascular risk markers and the other two inflammatory markers, SAA was found to be an independent risk factor for cardiovascular mortality after a short-term follow-up (6months-1year) with a HR per SD of 1.41. IL-6 was identified as an independent risk factor for long-term follow-up (3, 5, and 9.9years) with HRs per SD of 1.21, 1.22 and 1.18. CRP lost significance after adjustment. Although 6 out of 27 SAA SNPs were significantly associated with SAA plasma concentrations, the genetic risk score was not associated with cardiovascular mortality. The present findings from the large, prospective LURIC cohort underline the importance of inflammation in CAD and the prognostic relevance of inflammatory biomarkers that independently predict cardiovascular mortality.

Association between interleukin-4 and interleukin-10 single nucleotide polymorphisms and multiple sclerosis among Iraqi patients.

Multiple sclerosis (MS) is a neurodegenerative autoimmune disease, in which cytokines play a prominent role. Among these cytokines are interleukin-4 (IL-4) and IL-10, which have been demonstrated to be involved in immunopathogenesis of the disease. The present case-control study inspected the association between seven single nucleotide polymorphisms (SNPs) of IL4 (IL4-1098: rs2243248, IL4-590: rs2243250, and IL4-33: rs2070874), IL4RA (IL4RA+1902: rs1801275), and IL10 (IL10-1082: rs1800896, IL10-819: rs1800871, and IL10-592: rs1800872) genes and MS in Iraqi patients. Sixty-eight clinically definite relapsing-remitting MS Iraqi patients and 158 age- and gender-matched healthy control subjects were enrolled in the study. The SNPs were detected by the PCR-SSP (polymerase chain reaction-sequence specific primer) method. Results revealed that only IL4-1098, IL4-590, IL4-33, and IL10-592 SNP allele and/or genotype frequencies showed a significant variation between MS patients and control. At the haplotype level, the estimated frequency of TCC (IL4-1098-IL4-590-IL4-33) and GCC (IL10-1082-IL10-819-IL10-592) haplotypes was significantly increased in patients compared to control (TCC: 63.2 vs. 48.0%; odds ratio = 2.81; 95% confidence interval = 1.86-4.25; pc = 5.0 × 10-6; GCC 39.0 vs. 22.2%; odds ratio = 2.24; 95% confidence interval = 1.45-3.46; pc = 0.002). In conclusion, IL4 and IL10 genes harbor important SNPs that may confer MS susceptibility. In addition, their role in reducing the risk of disease is also suggested. However, the susceptibility of the investigated role can be better evaluated in terms of haplotype frequencies.

IL-4 polymorphism influences susceptibility to Pneumocystis jirovecii pneumonia in HIV-positive patients.

Objectives:Pneumocystis jirovecii pneumonia (PJP) is an important cause of morbidity and mortality in HIV-positive patients. Polymorphisms in immune genes are increasingly reported to influence susceptibility to fungal infections. We analysed the role of 21 single nucleotide polymorphisms from 19 candidate genes on PJP development in patients from the Swiss HIV Cohort Study.Design and methods:The analysis included patients with a nadir CD4+ T-cell count less than 200 cells/μl, divided into a discovery (N = 1645) and a replication (N = 1861) cohort. The associations were analysed by using cumulative incidence curves as well as competing risk regression over 18 years, starting from the estimated date of HIV infection, considering death a competing risk, with censoring at lost follow-up, and assuming the dominant mode of inheritance.Results:The minor allele of rs2243250 in IL-4 was associated with the risk of PJP in the discovery cohort (cumulative incidence 0.18 versus 0.12, P = 0.002). This association was replicated in the validation cohort (0.16 versus 0.12, P = 0.02). It was still significant in multivariate models, adjusted for HIV transmission mode, viral load, CD4+ T cells slope, age, antiretroviral therapy, tobacco smoking, hepatitis C virus coinfection, year of cohort entry and PJP prophylaxis (global subhazard ratio 1.42, 95% confidence interval 1.17–1.73, P = 0.0004).Conclusion:Our data suggest rs2243250, a single nucleotide polymorphism known to influence IL-4 production, is associated with susceptibility to PJP in HIV-positive patients.

Psoriasis: Association of interleukin-17 gene polymorphisms with severity and response to treatment.

Psoriasis is a chronic, inflammatory disease with a complex pathogenesis that is not yet fully understood. Although it is a multifactorial disease, the genetic factor has a major role in the pathogenesis of psoriasis. Genome wide association studies have identified over 50 genetic loci associated with psoriasis risk. Beside TNF-α or IL-23, the IL-17 family is a newer group that has proven implications in the pathogenesis of psoriasis. The most important members of the family, with pro-inflammatory qualities, are IL-17A and IL-17F. These interleukins are produced by a varied number of cells, but by far the most important are Th17 cells. Of the patients 20-30% present moderate-to-severe psoriasis, therefore, systemic medication (phototherapy, methotrexate, cyclosporine, acitretin or biologic agents) is mandatory. The necessity of an individualized treatment plan, for each patient, is imperative in order to establish the best strategy for non-responders to classical treatment or to other biologic treatments. The discovery of Th17 pathway improved the treatment and prognosis of psoriasis. Anti-psoriatic agents against IL-17 or its receptors are a novel group of biologic agents; these include ixekizumab, secukinumab and brodalumab. Polymorphisms of IL-17 family have been correlated with the severity and response to treatment in psoriasis, and also with the risk of inflammatory, infectious, autoimmune or neoplastic pathologies. The significant difference in the presence or absence of susceptibility loci in different population is due to genetic background and environmental factors that have a major impact on disease predisposition. In this study, we reviewed the importance and influence of the IL-17 polymorphisms as predictors of response to treatment and severity of the disease.

Polymorphisms in IL-10 and TGF-\u03b2 gene promoter are associated with lower risk to gastric cancer in a Mexican population

BackgroundHelicobacter pylori infection is recognized as the main risk factor for gastric cancer (GC), the fifth most common neoplasia worldwide. H. pylori interacts with the immune system, disrupting the cytokine network and inducing chronic inflammation. This work aimed to evaluate the association between single nucleotide polymorphisms (SNPs) in selected cytokine gene promoters and GC.MethodsThe study included 359 subjects, 125 GC patients, 109 intestinal metaplasia (IM) patients and 125 asymptomatic controls. DNA was extracted from white blood cells and nine SNPs in cytokine gene promoters were genotyped using predesigned 5′-endonulease assays. The association of the SNPs with IM and GC was evaluated using multinomial regression models.ResultsBoth genotypes, TC (OR = 0.51, 95% CI = 0.27–0.98) and TT (OR = 0.42, 95% CI = 0.20–0.91) in the locus − 509 of the TGF-β promoter were significantly associated with GC. The TT genotype in the locus − 819 of the IL-10 promoter was also significantly associated with GC (OR = 0.37, 95% CI = 0.17–0.81). No significant association was found with SNPs IL-4 –590 T/C (rs1800629), IL-6 –573G/C (rs1800796), IL-10 –592C/A (rs1800872), IL-10 –1082A/G (rs1800896), and, IFN-γ –1615C/T (rs2069705).ConclusionsSNPs in TGFβ (− 509 C/T, rs1800469) and IL-10 (− 819 C/T, rs1800871) promoters were associated with a lower risk for GC in a Mexican population.

Interleukin-17 Gene Polymorphism Is Protective Against the Susceptibility to Adult Acute Myeloid Leukaemia in Egypt: A Case-Control Study.

BACKGROUND:Th17 cells are blamed for being accused in the pathogenesis of acute myeloid leukaemia. Th17 cells are CD4+ cell subtype. They produce IL-17A and IL-17F.AIM:This study aims to trace the relation between IL-17A and IL-17F polymorphisms and AML incidence and to define the connection between IL-17 polymorphisms and its serum level.METHODS:A group of 100 acute myeloid leukaemia patients and 100 age and sex-matched healthy subjects (controls) were enrolled in the present work. Restriction fragment length polymorphism- polymerase chain reaction (PCR-RFLP) was done to detect IL-17A (rs2275913; G197A) and IL-17F (rs763780; A7488G). Serum IL-17 level was assessed by Enzyme-linked immunosorbent assay analysis (ELISA) in both patients and controls.RESULTS:IL-17F, IL-17A mutant genotypes and alleles showed no significant relation with acute myeloid leukaemia incidence. Also, ELISA results proved that serum IL-17 did not vary between acute myeloid leukaemia patients and healthy subjects.CONCLUSION:Interleukin-17 gene polymorphisms did not consider a risk for acute myeloid leukaemia.

Association between rs1800795 polymorphisms in the interleukin-6 gene and vasculitis: A meta-analysis.

Interleukin (IL)-6 is associated with the development and progression of vasculitis, and inhibitors of this cytokine are used to treat this disease. Polymorphisms of the promoter region of IL-6 are associated with the production and expression of IL-6. The aim of this study was to perform a meta-analysis of eligible studies to derive a precise estimate of the association between IL6 polymorphisms and susceptibility to vasculitis. A meta-analysis was conducted to identify the associations between IL6 rs1800795 (-174 G/C) polymorphisms and vasculitis. A total of 13 studies involving 1,294 vasculitis patients and 1,594 controls were considered in the meta-analysis. There were significant associations between IL6 rs1800795 polymorphisms and vasculitis in allele contrast, dominant genetic model, and heterozygote vs. dominant homozygote comparison (OR 0.80, 95% CI 0.67-0.94, P =0.009 and OR 0.76, 95% CI 0.63-0.92, P =0.005, respectively). In subgroup analysis based on subtype, there were significant associations between IL6 polymorphisms and susceptibility in large and medium vessel vasculitis, but not in small and variable vessel vasculitis. The GC genotype of IL6 rs1800795 was suggested by the analyses to be related to low prevalence of vasculitis, especially for large and medium vessels.

Su1074 – Association Between Single Nucleotide Polymorphisms in Il-1β, Il-6 and Il-10 and Early-Onset Colorectal Cancer in Puerto Rican Hispanics

Su1074 – Association Between Single Nucleotide Polymorphisms in Il-1β, Il-6 and Il-10 and Early-Onset Colorectal Cancer in Puerto Rican Hispanics

The relationship between single nucleotide polymorphisms and dental implant loss: a scoping review.

ObjectivesThe purpose of this review was to evaluate the relationship between genetic polymorphisms and dental implant loss.Materials and methodsAll case-control studies examining single nucleotide polymorphisms (SNPs) and dental implant failure were considered. A Boolean search was conducted on PubMed and Scopus to find eligible studies.ResultsThe initial search produced 78 results. Twenty-one studies were considered for inclusion after review and 16 were included in the final review. Twenty-two different polymorphisms were analyzed and statistically significant correlation was found for IL-4, IL-1A, IL-1B, MMP-8, and MMP-1 polymorphisms for dental implant failure.DiscussionA limited number of comprehensive studies have been done in this field. Additional studies with larger sample sizes and different ethnic backgrounds need to be done to see if the results can be reproduced. Of the polymorphisms studied, the IL-4 (+33), MMP-8 (−799), MMP-1 (−519), and MMP-1 (−1607) polymorphisms show the greatest association with dental implant loss.

A functional polymorphism in the promoter region of IL-33 is associated with the reduced risk of colorectal cancer.

Aim: We aimed to investigate IL-33 polymorphisms with risk of colorectal cancer (CRC). Materials & methods:IL-33 rs7025417 and rs1332290 were genotyped using a quantitative allelic Taqman assay. The expression of IL-33 mRNA was determined by real-time PCR and promoter activity was assayed using the Dual-Luciferase Reporter Assay. Results: The IL-33 rs7025417 CC genotype and C allele may decrease CRC risk. The IL-33 rs1332290 AC carriers had an increased risk of developing clinical Stage III-IV CRC. Lower levels of IL-33 mRNA were present in individuals with the rs7025417 CC genotype. Moreover, the rs7025417 C allele suppressed promoter activity of IL-33. Conclusion: These data suggest that the rs7025417 CC genotype may downregulate IL-33 mRNA and subsequently reduce the risk of CRC.

Long-range cis-regulatory architecture of the human IL2 gene

Abstract Interleukin-2 is a potent T cell growth factor with crucial roles in both immunity and tolerance. The IL2 gene is regulated by multiple signaling pathways, transcription factors, and epigenetic processes operating at the 500 bp upstream regulatory region (URR). Genome-wide association studies (GWAS) in humans have shown that genetic variation in the IL2 region is associated with susceptibility to autoimmune diseases. This region harbors several conserved noncoding sequences. We are performing a comprehensive epigenomic and functional interrogation of the human IL2-IL21 multi-locus region, using a combination of open chromatin mapping (ATAC-seq), recombinant promoter-reporter assays, 3-dimensional chromosome conformation capture (Capture-C), and CRISPR/CAS9 genome editing. ATAC-seq analysis identified TCR/CD28 activation-dependent chromatin remodeling at −46, −51, −80, −83, −-85, −121, and −128 kb upstream of IL2 in human T cells. Chromatin conformation capture indicates that several of these distal regions physically interact with IL2, and are capable of enhancing transcription from the IL2-URR in recombinant reporter assays. The −128 kb element showed autoimmune disease-associated allelic variation in enhancer activity, and CRISPR/CAS9-mediated deletion of this element in human T cells resulted in a 2–3 fold reduction in activation-induced IL-2 production. These results suggest that the IL2 locus has evolved an extensive regulatory architecture that allows for variable production of IL-2, and provide insight into why most autoimmune IL2 polymorphisms are located far away from the gene.

IL18 Polymorphism and Periodontitis Susceptibility, Regardless of IL12B, MMP9, and Smoking Habits.

Genetic variations contribute to the susceptibility in the development of periodontitis. The aim of this study was to investigate the influence of IL18, IL12, and MMP9 polymorphisms in the chronic periodontitis. This case-control study involved 381 individuals matched by gender and age. Genotyping of IL18 (rs187238 and rs1946518) and IL12B (rs3212227) was performed by PCR-SSP and PCR-RFLP was used for MMP9 (rs3918242). IL-18 and MMP-9 were quantified in the serum by ELISA. SNPStats and OpenEpi software were used for statistical analysis and, in order to eliminate smoking as a confounding factor, the analyses were also performed in nonsmoking subjects. The IL18-137G/C genotype was associated with the risk of chronic periodontitis in nonsmokers (Pc = 0.03; OR = 1.99; overdominant inherence model). In the multivariate analyses, homozygous IL18-137G/G and IL18-607C/C were more frequent in males compared to women with these same genotypes (OR = 2.51 and OR = 3.30, respectively). The serum levels of the IL-18 in patients were higher than those in healthy controls (P = 0.005). IL12B and MMP9 polymorphisms and MMP-9 serum concentration were similar in patients and controls. In this study, IL18 was associated with chronic periodontitis susceptibility. Men had greater risk than women for developing the disease when IL18 polymorphism was considered and the susceptibility was independent of the smoking status.