IL-10 Promoter Polymorphisms Research Articles

PO-0186 Influence Of Il-10 Gene Polymorphisms On Immune Responses After Acellular Pertussis Booster Vaccination In Adolescents: Abstract PO-0186 Table 1

Background and aim Despite the mass vaccinations, pertussis has recently caused large epidemics in many industrialised countries. Vaccine-induced immune responses may be impaired due to polymorphisms in genes encoding regulatory cytokines such as IL-10. The aim of this study was to evaluate the role of IL-10 promoter polymorphisms on vaccine responses after acellular pertussis booster vaccinations. Methods Seventy-five adolescents received diphtheria-tetanus-acellular pertussis (dTap) vaccination in 1997. They were followed at 3, 5 and 10 years after. At year 10, a second booster was administrated. Antibodies (n = 52) and cell mediated immunity (CMI) (n = 38) against pertussis antigens were measured. IL-10 polymorphisms (rs1800890 and rs1800896) were detected using Sequenom iPlex Gold system. Results After the second booster, rs1800896 was found to affect the geometric mean value (GMV) of proliferation (counts per minute, cpm) and stimulation index (SI) against pertussis antigens; pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (PRN) (Table). Another SNP (rs1800890) affected the CMI against PT and FHA after the booster vaccination. Also, the IgG antibody concentration against PT and PRN differed significantly between the genotypes after the original vaccination, at 3-year follow-up and before the second booster. Conclusion These preliminary results suggest that IL-10 might play an important role in modulating both antibody and cell mediated immune responses after pertussis vaccination.

Functional polymorphisms of interleukin-18 gene and risk of breast cancer in a Brazilian population.

Interleukin-18 (IL-18) is a key cytokine responsible for immune response and involved in the process of cancer development. In this case-control study, we tested whether IL-18 promoter polymorphism contributes to breast cancer susceptibility in Brazilian patients. The two groups studied were 154 patients with breast cancer and 118 healthy individuals. The frequency of IL-18 promoter single nucleotide polymorphisms (SNPs) at positions -607 (C/A) (rs1946518) and -137 (G/C) (rs187238) was determined by polymerase chain reaction analyses. The polymorphisms genotyped in this study showed a significant association with breast cancer under different genetic models. Both SNPs showed a positive association. For the IL18-607 polymorphism the best model was the codominant genetic model [CC vs AA, P = 0.004, odds ratio (OR) = 2.782, 95% confidence interval (CI) 1.385-5.589]. For IL18-137 statistical significance was found using the recessive genetic model (P = 0.008, OR = 3.896, 95% CI 1.427-10.639). The association between the haplotypes of the IL18 gene and breast cancer was further confirmed. Our results suggest that IL18-607 and IL18-137 polymorphism contributes to increase the breast cancer risk. To our knowledge, this is the first report regarding Brazilian breast cancer patients and IL18 promoter polymorphisms.

Cytokine Gene Considerations in Giant Cell Arteritis: IL10 Promoter Polymorphisms and a Review of the Literature

Polymorphisms of cytokine genes have been investigated as susceptibility markers of giant cell arteritis (GCA). Here, we have reviewed the evidence to date and especially addressed the functional consequences of IL10 (-592C/A and -1082A/G) gene polymorphisms and their association with susceptibility to and disease phenotype in GCA. A total number of 71 patients with GCA and 124 age-matched controls were genotyped using allele-specific primers and restriction fragment length polymorphism analysis. As previous studies in GCA showed inconsistent results, a meta-analysis of the existing studies was also conducted by using both fixed and random-effects models. The levels of circulating IL10 and the production of IL10 by peripheral blood mononuclear cells after in vitro stimulation were studied by Cytometric Bead Array. Data showed no significant differences in genotype or allele frequency distribution between patients and controls. The clinical characteristics and prognosis of these patients were also unrelated to the presence of these polymorphisms. However, the meta-analysis found a significant association of IL10 -592C/A polymorphism with susceptibility to GCA (odds ratio 2.205 (95% confidence interval 1.074-4.524); p = 0.031). In both patients and age-matched controls, no differences in circulating IL10 levels or IL10 production were observed depending on the genotypes of the IL10 gene. In conclusion, although our cohort results do not support the impact of IL10 variants in susceptibility or clinical phenotype of GCA patients, the meta-analysis revealed a significant association of -592C/A polymorphism with susceptibility to GCA. In this population, no functional association was found between IL10 gene variants and IL10 production.

Role of TGF beta and il-18 promoter polymorphism in association with lung cancer

Lung cancer is the number one cause of cancer-related deaths in the world. World Health Organization classified it into two main histological groups such as non-small cell lung cancer and small-cell lung cancer. Its incidence is highly correlated with cigarette smoking, among the 10% of patients who develop it without a smoking history, the environmental or inherited causes of this is usually unclear. These are most predominant as the cancer is a multistep, progressive disease and early chromosomal changes provide the cell with proliferative advantage. The role of TGF beta in association with pulmonary tumorigenesis and inhibition is a hallmark of multiple cancers including lung cancer. Restoration of this TGF beta signalling reduces tumorigenicity in human lung cancer cells. The present study undergone to assess the role of TGF beta and IL-18 promoter polymorphism in association with lung cancer by molecular and cytogenetic studies in lung cancer patients. The results were compared with the healthy population series. It was found that the recessive allele T in TGF Beta and A/A frequency at the position -607 of IL 18 is considerably and significantly higher in patients. There were no abnormalities derived from the cytogenetic study.

Interleukin-18 promoter polymorphisms and plasma levels are associated with increased risk of periodontitis: a meta-analysis

Emerging evidence has showed that interleukin-18 (IL-8) promoter polymorphisms and plasma IL-18 levels may be associated with increased risk of periodontitis, but individually published results are inconclusive. The aim of this meta-analysis was to derive a more precise estimation of these associations. A literature search of PubMed, Cochrane Library, Embase, Web of Science, SpringerLink, China BioMedicine and China National Knowledge Infrastructure databases was conducted on articles published before April 1st, 2013. Crude odds ratio (OR) or standardized mean difference (SMD) with 95 % confidence intervals (CI) were calculated. Nine case-control studies were included with a total of 576 periodontitis patients and 458 healthy controls. Two common polymorphisms (-607A > C and -137G>C) in the IL-18 gene were addressed. Our meta-analysis results indicated that the C variant of IL-18 -607A>C polymorphism was associated with increased periodontitis risk (C allele vs. A allele: OR = 1.86, 95 % CI: 1.30-2.65, P = 0.001; AC+CC vs. AA: OR = 2.64, 95 % CI: 1.34-5.21, P = 0.005). There was also a significant association between the C variant of IL-18 -137G>C polymorphism and an increased periodontitis risk (C allele vs. G allele: OR = 1.47, 95 % CI: 1.13-1.91, P = 0.004; GC+CC vs. GG: OR = 1.66, 95 % CI: 1.21-2.29, P = 0.002). Furthermore, the mean levels of plasma IL-18 of periodontitis patients were also higher than those of healthy controls (SMD = 1.18, 95 % CI: 0.51-1.85, P = 0.001). The current meta-analysis suggests that IL-18 promoter polymorphisms and plasma IL-18 levels are associated with increased risk of periodontitis. IL-18 promoter polymorphisms and elevated plasma IL-18 levels may be useful biomarkers for predicting the development of periodontitis.

Interleukin 10 gene promoter polymorphism and risk of diffuse large B cell lymphoma (DLBCL)

PurposeGiven the importance of understanding the genetic variations involved in the pathogenesis of non-Hodgkin’s lymphoma (NHL), this work was designed to study the impact of IL-10 (−1082 G/A; rs1800896 and −819 C/T; rs1800871) gene promoter polymorphism on susceptibility of Egyptians to diffuse large B cell lymphoma (DLBCL); the major type of NHL. To the best of our knowledge, this study is the first one that examines IL-10 promoter polymorphism in DLBCL in Egyptians. MethodsGenotyping polymorphism is performed using sequence-specific primers polymerase chain reaction (SSP-PCR) in 100 Egyptian DLBCL patients and 119 normal controls. Circulating plasma levels of IL-10 were measured using Enzyme-linked immunosorbent assay (ELISA). ResultsInsignificant change in IL-10 (−1082 and −819) genotypes was recorded. Although A allele is slightly decreased in DLBCL patients, it did not reach statistical significance. GT haplotype was significantly elevated (P<0.05) in NHL patients. A significant linkage disequilibrium between the −1082 and −819 SNPs with D′=0.596 and r2=0.1032 (P<0.001) was demonstrated. Significantly increased plasma IL-10 (P<0.01) was found which is positively correlated (r=0.307; P<0.01) with the disease. ConclusionsTaken together, our findings demonstrated that IL-10 promoter gene polymorphism (−1082 and −819) may not have an influence on the clinical outcome of DLBCL, especially in terms of overall secretion level. Further investigations of other cytokine gene polymorphisms will lead to a better understanding of the disease’s biological background.

The association between interleukin-6 gene polymorphisms and intracranial aneurysms: A meta-analysis

BackgroundInterleukin-6 (IL-6) is an important proinflammatory cytokine, and some studies have demonstrated that IL-6 promoter polymorphisms (−174G/C and −572G/C) may be associated with intracranial aneurysms. A meta-analysis based on the evidence currently available from the literature was conducted to make a more precise estimation of this relationship. MethodsElectronic databases (the National Library of Medline and Embase databases) were searched before June 2013. Odds ratio (OR) and 95% confidence interval (CI) were calculated in fixed- or random-effects models when appropriate. Subgroup analyses were performed by race. This meta-analysis included six case-control studies, which included 1188 intracranial aneurysms cases and 4099 controls. ResultsThe combined results based on all studies showed that intracranial aneurysms cases had a significantly lower frequency of −572CC [OR (Recessive model)=0.47, 95% CI=0.36, 0.60, P<0.001; OR (Codominant model)=0.29, 95% CI=0.20, 0.44, P<0.001], −572GC [OR (Codominant model)=0.73, 95% CI=0.55, 0.98, P=0.04] and −174CC [OR (Recessive model)=0.73, 95% CI=0.54, 0.98, P=0.03; OR (Codominant model)=0.70, 95% CI=0.51, 0.97, P=0.03] genotype. In the subgroup analysis by race, we found that (1) intracranial aneurysms cases had a significantly lower frequency of −572CC [OR (Recessive model)=0.41, 95% CI=0.32, 0.53, P<0.001; OR (Codominant model)=0.18, 95% CI=0.12, 0.29, P<0.001] and −572GC [OR (Codominant model)=0.61, 95% CI=0.42, 0.88, P=0.009] genotype in Asians; (2) intracranial aneurysms cases had a significantly higher frequency of −572CC [OR (Recessive model)=4.41, 95% CI=1.35, 14.36, P=0.01; OR (Codominant model)=4.41, 95% CI=1.35, 14.38, P=0.01] genotype and lower frequency of −174CC [OR (Recessive model)=0.73, 95% CI=0.54, 0.98, P=0.03; OR (Codominant model)=0.70, 95% CI=0.51, 0.97, P=0.03] genotype in Caucasians. ConclusionsOur meta-analysis suggested that IL-6 promoter polymorphisms (−174G/C and −572G/C) were associated with intracranial aneurysms. However, due to the small subjects included in analysis and the selection bias in some studies, the results should be interpreted with caution.

The association of interleukin-18 promoter polymorphisms and serum levels with duodenal ulcer, and their correlations with bacterial CagA and VacA virulence factors

We analyzed the impact of interleukin (IL)-18 promoter polymorphisms on IL-18 serum levels in Helicobacter pylori-infected duodenal ulcer (DU) patients and healthy asymptomatic (AS) carriers. We also aimed to determine the association of the H. pylori virulence factors CagA and VacA antibodies with serum concentrations of IL-18 in order to elucidate any correlation between them. Three groups of patients were enrolled: DU patients (67 individuals), AS carriers (48 individuals), and H. pylori-negative subjects (26 individuals). Serum concentrations of IL-18 were determined by ELISA. Patient sera were tested by Western blot method to determine the presence of serum antibodies to bacterial CagA and VacA. Genotyping of IL-18 promoter polymorphisms at positions - 137G/C and - 607C/A were performed by allele-specific primer PCR protocol. Our study revealed that serum IL-18 levels are positively influenced by CagA-positive H. pylori strains, so that maximum levels of IL-18 were detected in DU patients with the CagA(+) phenotype, regardless of the presence of the anti-VacA antibody. Regarding IL-18 promoter polymorphisms, the AA genotype and A allele at position - 607C/A were found to be significantly lower in DU patients than in AS carriers and H. pylori-negative subjects (p = 0.032 and 0.043, respectively). The IL-18 - 607C variant was associated with higher levels of serum IL-18 and an increased risk of DU. Moreover, our findings indicated that serum concentrations of IL-18 were influenced by CagA factor, irrespective of the VacA status, suggesting that high levels of IL-18 in CagA-positive subjects predisposes to susceptibility to DU.

AB0250 IL-6, IL-10 and PTPN22 gene polymorphism in children with juvenile idiopathic arthritis

BackgroundJuvenile idiopathic arthritis (JIA) is heterogenous group of diseases and it is most common rheumatic disease in children. Inflammatory cytokines and their regulatory gene polymorphisms are important in the pathogenesis...

SP0038 Chronic nonbacterial osteomyelitis

Chronic nonbacterial osteomyelitis CNO is an inflammatory disorder of the musculoskeletal system with yet unknown etiology. In addition to bone inflammation, patients may present with inflammation of other tissues including...

IL-10 promoter polymorphism associated with decreased risk of aGvHD after stem cell transplantation: a meta-analysis

The bulk of evidences indicates that variations in the coding for cytokines or the regulation of their expression may play a role in acute graft-versus-host disease (aGvHD) following allogeneic hematopoietic stem cell transplantation (HSCT). It is unclear whether IL-10 promoter polymorphism is associated with the occurrence of aGvHD in allogeneic HSCT. A systematic search was performed in PubMed and Embase databases and 10 studies were identified for inclusion. Data were extracted and pooled ORs together with 95% CIs were calculated. The pooled result indicated that -592A allele in recipient was significantly associated with reduced risk of moderate aGvHD in HSCT [OR = 0.41 (0.21, 0.79), P = 0.008, I² = 25%]. The same pattern was also obtained from the -819T allele in recipient [OR = 0.38 (0.18, 0.79), P = 0.01, I² = 41%]. Furthermore, we found a significant positive correlation between the -592AA homozygote and lower risk of severe aGvHD in HSCT [OR = 0.54 (0.34, 0.86), P = 0.01, I² = 29%]. The similar result was gained from the -1082A allele in recipient and decreased risk of severe aGvHD [OR = 0.71 (0.52, 0.98), P = 0.04, I² = 19%]. However, there was no significant association between -592A, -819T, or -1082A allele in donor and risk of aGvHD. This meta-analysis suggests that the IL-10 A allele or AA homozygote at -592, T allele at -819 and the A allele at -1082 are associated with reduced risk of aGvHD in allogeneic HSCT.

No correlation between interleukin-10 gene promoter polymorphisms and hepatitis B virus infection outcome.

BackgroundSingle nucleotide polymorphisms (SNP) in the promoter region of the interleukin (IL)-10 genes have a role in determining hepatitis B virus (HBV) outcome.ObjectivesThis study evaluates the correlation between HBV infection and SNP in IL-10 gene promoter.Patients and MethodsNinety-six HBV-infected patients (32 chronic hepatitis B infection patients, 34 healthy carriers, 30 spontaneously recovered cases) and 31 healthy controls were enrolled. Three biallelic (-819,-592,-1082) regions in the IL-10 gene promoter were sequenced for all patients.ResultsGenotypes and haplotypes of IL-10 gene promoter region at position -1082, -819 and -592 were not significantly different among controls, HBV recovered cases, carriers and chronic HBV patients. Nevertheless, A/A genotype at position -592 and T/T genotype at position -819 were more frequently seen in the HBV clearance group, while frequency of G/G genotype at position -1082 was more prevalent in the persistence group. GCC/GCC and GCC/ACC haplotypes were significantly observed in anti-HBe positive individuals.ConclusionsOur findings showed that IL-10 promoter polymorphisms were not correlated with HBV infection prognosis. Nevertheless, individuals carrying high and intermediate producer of IL-10 haplotypes had a better ability to develop anti-HBe than low producer carriers.

Interleukin-10 Gene Promoter Polymorphisms and Risk of Gastric Cancer in a Chinese Population: Single Nucleotide and Haplotype Analyses

Interleukin (IL) -10 is a potent cytokine with a dual ability to immunosuppress or immunostimulate. We aimed to explore the association of IL10 promoter polymorphisms with risk of gastric cancer (GC) in a Han population in Southwestern China. We enrolled 308 pairs of GC and control subjects from four hospitals and a community between October 2010 and August 2011 in a 1:1 matched case-control design. Demographic information was collected using a designed questionnaire. IL10-592 A>C and IL10-1082 A>G polymorphisms were determined by Sequenom MassARRAY analysis. Patients with GC reported statistically higher proportions of family history of cancer (29.9% versus 10.7%, P<0.01) and alcohol drinking (54.6% versus 43.2%, P<0.01) than did controls. Similar results were observed in comparison between non-cardia GC patients and controls (P<0.01 and P=0.03). Variant genotypes of IL10-592 A>C and IL10-1082 A>G were not associated with overall GC risk (adjusted OR, 0.94, 95% CI, 0.66-1.33; adjusted OR, 1.00, 95% CI, 0.62-1.60). Sub-analysis showed that the IL10-592 AC/CC variant genotype was associated with decreased non-cardia GC risk (adjusted OR, 0.58; 95% CI, 0.36-0.95). No association was found between any of the IL10 haplotypes established from two polymorphisms and risk of non-cardia GC. In conclusion, our data do not link the two SNPs of IL10-592 and IL10-1082 with overall GC risk. We demonstrate that IL10-592 polymorphism is associated with protective effect against non-cardia GC. Our findings may offer insight into risk associated with the development of GC in this region.

Promoter polymorphisms of the TNF a (-308 G/A) and IL-6 (-174G/C) genes predict therapeutic response to etanercept

Event Abstract Back to Event Promoter polymorphisms of the TNF α (-308 G/A) and IL-6 (-174G/C) genes predict therapeutic response to etanercept Ivan Jančić1*, Nevena Arsenović-Ranin1, Mirjana Šefik-Bukilica2, Slađana Živojinović2, Nemanja Damjanov2, Vesna Spasovski3, Sanja Srzentić3, Biljana Stanković3 and Sonja Pavlović3 1 Faculty of Pharmacy, University og Belgrade, Serbia 2 Institute of Rheumatology, Serbia 3 Institute of Molecular Genetics and Genetic Engineering, Serbia The aim of the study was to explore putative influence of - 308 G/A TNFα and –174 G/C IL-6 promoter polymorphisms (releated to TNFα and IL-6 level) on the therapeutic response to etanercept, a TNFα blocker, in patients with rheumathoid arthritis (RA). 73 patients suffering from active RA were examined at the begining of etanercept treatment and 6- and 12-months following the begining of the treatment. The therapeutic response was estimated according to the European League Against Rheumatism response criteria. Patients were genotyped for –308 G/A TNFα and –174 G/C IL-6 gene polymorphisms by the PCR-RFLP method, and influence of the genotype to clinical response to etanercept was assessed. Association between –308 G/A TNFα polymorphism and a response to etanercept after 6 and 12 months of therapy was not found. After 12 months the percentage of responders (patients who had DAS28 improvement > 1.2) was significantly increased in patients with the –174 GG IL-6 genotype (95.7 %) compared with those with the –174 GC IL-6 (75.6 %) and –174 CC IL-6 (44.4 %) genotype (p = 0.006). The best responders after 12 months were patients with –308 GG TNFα/–174 GG IL-6 genotype combination compared to the other genotype combinations (p = 0.022). The patients with RA exhibiting –308 GG TNFα/–174 GG IL-6 genotype respond better to etanercept than patients with other genotypes examined. This finding suggests that this polymorphism combination should be considered as a genetic marker of responsiveness to TNFα blockers in RA. Keywords: - 308 G/A TNFα promoter polymorphism, –174 G/C IL-6 promoter polymorphism, ra, etanercept, das28 responders Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Immune-mediated disease pathogenesis Citation: Jančić I, Arsenović-Ranin N, Šefik-Bukilica M, Živojinović S, Damjanov N, Spasovski V, Srzentić S, Stanković B and Pavlović S (2013). Promoter polymorphisms of the TNF α (-308 G/A) and IL-6 (-174G/C) genes predict therapeutic response to etanercept. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00173 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 11 Mar 2013; Published Online: 22 Aug 2013. * Correspondence: Mr. Ivan Jančić, Faculty of Pharmacy, University og Belgrade, Belgrade, Serbia, ijancic@pharmacy.bg.ac.rs Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Ivan Jančić Nevena Arsenović-Ranin Mirjana Šefik-Bukilica Slađana Živojinović Nemanja Damjanov Vesna Spasovski Sanja Srzentić Biljana Stanković Sonja Pavlović Google Ivan Jančić Nevena Arsenović-Ranin Mirjana Šefik-Bukilica Slađana Živojinović Nemanja Damjanov Vesna Spasovski Sanja Srzentić Biljana Stanković Sonja Pavlović Google Scholar Ivan Jančić Nevena Arsenović-Ranin Mirjana Šefik-Bukilica Slađana Živojinović Nemanja Damjanov Vesna Spasovski Sanja Srzentić Biljana Stanković Sonja Pavlović PubMed Ivan Jančić Nevena Arsenović-Ranin Mirjana Šefik-Bukilica Slađana Živojinović Nemanja Damjanov Vesna Spasovski Sanja Srzentić Biljana Stanković Sonja Pavlović Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

The Role of Interleukin 18 Promoter Polymorphisms ( -607 C/A and 137 G/C ) in Determining HCV Clearance or Persistence

Objective: Two interleukin (IL-18) Polymorphisms ( - 607 C/A and -137 G/C ) and their haplotypes are known to affect the IL-18 expression. A number of SNPs ( single nucleotide polymorphisms ) that influence IL- 18 production are found in the gene promoter region. Aim of the work: The study will determine HCV clearance or persistence as a result of IL-18 promoter polymorphisms (-607 C/A and 137 G/C ) in chronic hepatitis C virus infected patients during interferon and ribavirin treatment. Patients and methods: Eighty patients with chronic hepatitis C virus infection, their age ranges between (23-57) years, selected from the National Hepatology and Tropical Medicine Research Institute were included in this study, during interferon and ribavirin therapy and fifteen healthy individuals were included to serve as controls. All the patients and controls were subjected to the following history, clinical examination, abdominal ultrasonography and collection of blood samples for routine laboratory investigation, CBCs and serological assay and specific sequence primer polymerase chain reaction (PCR) IL-18-137, 607 SNP. Results: There was no significant difference in the frequencies of -137 allelic distribution in CHCV infection patients and healthy controls. The -607 AA allele was higher among controls than in patients with CHCV infection. The -607 CC allele was higher among the CHCV patients than in the healthy controls. 87.5 % of the studied CHCV patients had response to IFN therapy, the majority of cases had A1F1 biopsy results. Conclusion: IL-18 promoter polymorphism at -607 position with AA allele is a potential protective marker, as it is higher among healthy controls than the CHCV patients. Recommendations: that IL-18 could be considered as a target for therapeutics.

Association of interleukin‐18 promoter polymorphisms with chronic obstructive pulmonary disease in male smokers

Chronic obstructive pulmonary disease (COPD) is considered a complex genetic disorder and it is expected that many genes play a role in the pathogenesis of this disease. Previous studies have reported that several variations within the interleukin (IL)-18 gene promoter region have been associated with different inflammatory diseases such as asthma. However, the association of IL-18 promoter polymorphisms with COPD has not been studied yet. We then performed a prospective case-control study to explore this association in male smokers of Chinese Han people. Our study recruited 112 COPD cases and 105 healthy controls matched for age. The genotyping of IL-18 promoter polymorphisms (-607 C/A and -137 G/C) was performed using TaqMan single nucleotide polymorphism genotyping assays. The frequencies of the alleles and genotypes in patients and controls were compared. We found that the frequency of IL-18 -607 C allele was significantly increased in patients with COPD (odds ratio (OR) = 1.48, 95% confidence interval (CI) = 1.01-2.15, P = 0.04). The frequency of IL-18 -607 C allele was significantly higher in the GOLD (Global initiative for Obstructive Lung Disease) 3-4 group compared with the GOLD 1-2 group (OR=2.06, 95% CI = 1.21-3.51, P = 0.01). There were no significant differences in the frequencies of the alleles and genotypes of IL-18 -137 G/C polymorphism between the patients and healthy smokers or between GOLD 3-4 group and GOLD 1-2 group. Our study revealed that the IL-18 -607 C/A polymorphism was associated with COPD susceptibility and severity of airflow limitation in male smokers of Chinese Han people.

The SNP at -592 of human IL-10 gene is associated with serum IL-10 levels and increased risk for human papillomavirus cervical lesion development.

BackgroundWomen with Human Papilloma Virus (HPV) persistence are characterized by high levels of IL-10 at cervix. We have determined whether polymorphisms of IL-10 gene promoter might be associated with increased risk of squamous intraepithelial cervical lesions (SICL) and whether exist significative differences of IL-10 mRNA expression at cervix and systemic and serum IL-10 protein between SICL cases and non-Cervical Lesions (NCL).MethodsPeripheral blood samples from SICL (n = 204) and NCL (n = 166) were used to detect IL-10 promoter polymorphisms at loci -592A/C (rs1800872), -819C/T (rs1800871), -1082A/G (rs1800896), -1352A/G (rs1800893), by allelic discrimination and to evaluate serum IL-10 protein. Cervical epithelial scrapings from NCL and biopsies from SICLs were used for HPV-typing and to evaluate IL-10 mRNA expression level. The systemic and local IL-10 mRNA expression levels were measured by real time-PCR. Genotypic and allelic frequencies of the selected polymorphisms were analyzed by logistic regression, adjusting by age and HPV-genotype, to determine the association with SICL.ResultsNo significant differences were found between genotype frequencies at loci −819, -1082, and −1352. Individuals carrying at least one copy of risk allele A of polymorphism −592 had a two-fold increased risk of developing SICL [adjusted odds ratio (OR), 2.02 (95% CI, 1.26-3.25), p = 0.003], compared to NCL. The IL-10 mRNA expression and serum IL-10 protein, were significantly higher in SICL cases (p < 0.01), being higher in patients carrying the risk allele A.ConclusionsThe −592 polymorphism is associated with increased risk of SICL and can serve as a marker of genetic susceptibility to SICL among Mexican women. According to IL-10 levels found in SICL, IL-10 can be relevant factor for viral persistence and progression disease.

Interleukin-6 Gene Promoter-572 C Allele May Play a Role in Rate of Disease Progression in Multiple Sclerosis

Multiple sclerosis (MS) is an inflammatory demyelinating disease affecting the central nervous system. Although the exact pathogenesis of MS is unknown, it is generally considered to be an autoimmune disease, with numerous genetic and environmental factors determining disease susceptibility and severity. One important mediator of immune responses and inflammation is interleukin-6 (IL-6). Previously, elevated levels of IL-6 in mononuclear cells in blood and in brain tissue from MS patients have been reported. Various polymorphisms in the promoter region of the IL6 gene have also been linked with IL-6 protein levels. In MS, several small studies have investigated whether two IL6 promoter polymorphisms (−597 G>A and −174 G>C) correlate with MS susceptibility, but with varying results. In the present study, we analyzed these polymorphisms, together with an additional polymorphism (−572 G>C) in 279 healthy controls and 509 patients with MS. We found no significant differences between MS patients and healthy controls for the different −597 or −174 IL6 promoter alleles or genotypes. There was a slight reduction in the percentage of individuals with MS who carried a C allele at position −572, although this was not significant after correction for multiple comparisons. Interestingly, however, the −572 C allele showed a significant correlation with the MS severity score, suggesting a possible role in disease progression.

Is the IL-10 Promoter Polymorphism at Position -592 Associated with Immune System-Related Diseases?

Immune responses are the main causes of immune system-related diseases such as hypersensitivities and autoimmunity. It has also been established that cytokines play key roles in the regulation of immune responses which have been shown to be important in the pathogenesis of the diseases. IL-10, the main anti-inflammatory cytokine, is produced by several immune cells such as T regulatory and Th2 lymphocytes, activated macrophages, B regulatory lymphocytes as well as other cell types. It plays a key role in the regulation of immune responses after microbe elimination (homeostasis) and against self-antigens to prevent hypersensitivity and autoimmune diseases, respectively. Studies showed that a single nucleotide polymorphism (SNP) at the -592 position of IL-10 is associated with its regulation of expression. This review addresses the recent information regarding the association of the polymorphism at position -592 of IL-10 with immune-related diseases including type 2 diabetes with and without nephropathy, multiple sclerosis, and asthma with an emphasize on Iranian patients.

Interleukin-10 Haplotype May Predict Survival and Relapse in Resected Non-Small Cell Lung Cancer

IL-10 is associated with tumor malignancy via immune escape. We hypothesized that IL-10 haplotypes categorized by IL-10 promoter polymorphisms at –1082A>G, –819C>T, and –592C>A might influence IL-10 expression and give rise to non-small cell lung cancer (NSCLC) patients with poor outcomes and relapse. We collected adjacent normal tissues from 385 NSCLC patients to determine IL-10 haplotypes by direct sequencing and polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Of the 385 tumors, 241 were available to evaluate IL-10 mRNA expression levels by real-time RT-PCR. The influence of IL-10 haplotypes on overall survival (OS) and relapse free survival (RFS) were determined by Kaplan-Meier and multivariate Cox regression analysis. The results showed that IL-10 mRNA levels were significantly higher in tumors with the non-ATA haplotype than with the ATA haplotype (P = 0.004). Patients with the non-ATA haplotype had shorter OS and RFS periods than did patients with the ATA haplotype. This may be associated with the observation that the number of tumor-infiltrating lymphocytes was decreased in the tumors with higher levels of IL-10. Consistently, T cells from the peripheral blood of the patients with non-ATA haplotype were more susceptible to apoptosis and less cytotoxic to tumor cells, compared to those from the patients with ATA haplotype. The results suggest that IL-10 can promote tumor malignancy via promoting T cell apoptosis and tumor cell survival, and IL-10 haplotype evaluated by PCR-RFLP or direct sequencing may be used to predict survival and relapse in resected NSCLC, helping clinicians to make appropriate decisions on treatment of the patients.