IL-1RN Gene Polymorphisms Research Articles

Abstract P123: IL1RN Gene Polymorphism And The Development Of Acute Myocardial Infarction In Young Patients

IL-1RA is a member of the interleukin-1 cytokine family. IL1Ra is secreted by various types of cells, including immune cells, epithelial cells, and adipocytes, and is a natural inhibitor of the pro-inflammatory effect of IL1. This protein inhibits the activity of interleukin 1, alpha (IL1A) and interleukin 1, beta (IL1B) and modulates various interleukin 1-related immune and inflammatory responses. Hypothesis: The aim of this study was to investigate the relationship between IL1RN gene polymorphism and the development of acute myocardial infarction (AMI) in young patients. Material/methods: In a case-control study, we investigated polymorphisms in the IL1RN gene (rs4251961) using quantitative real-time polymerase chain reaction analysis. The study was conducted with AMI (age range: 36 to 55 years; mean: 42.74 ± 12.47 years) with 11 healthy people in the control group. We also studied the interaction between genetic polymorphism and inflammatory agents such as CRP, IL 1, IL 6. All indicators were calculated using the statistical program Statistica 12.0, a P-value <0.05 was considered statistically significant. Results: Statistically significant differences in the distribution of rs4251961 genotypes were observed between the two groups. Carriers of the T allele had a significantly higher risk of developing AMI than carriers of the C allele (P <0.05). Subjects carrying the TT and TC haplotypes have a significantly increased incidence of coronary artery disease. We also found that the CYP1B1 rs1056836 polymorphism had a synergistic effect with CRP levels on the risk of coronary heart disease. Conclusions: The rs4251961 gene polymorphism is closely associated with the development of AMI in patients with coronary artery disease. There is a mutual synergistic effect between the inflammatory response and IL1RN gene polymorphism in relation to the development of CAD complications. Functional polymorphisms of the IL1RN gene can affect the susceptibility and progression of CAD, increase the pro-inflammatory response, and destabilize the atherosclerotic plaque.

Association between IL1RN gene polymorphisms and post-stroke infection

Association between IL1RN gene polymorphisms and post-stroke infection

External Apical Root Resorption and IL-1A, IL-1RN Gene Polymorphisms: A Systematic Review and Meta-Analysis of Prospective Studies

Objective: To reconnoiter the IL-1A (-889) and IL-1RN (+2018) gene polymorphisms and their association with EARR . Material and Methods: The Science Direct, PubMed and Scopus databases were comprehensively searched by two independent reviewers. In addition, the bibliographies of all relevant publications and textbooks were searched manually. A meta-analysis was performed using data available up to May 9, 2020. Results: A total of 13 and 9 publications were selected for the systematic review and meta-analysis, respectively for both IL-1A and IL-1RN genes. Odds ratio (OR) was used to evaluate the association of the gene polymorphism and the risk of EARR. The risk of EARR was estimated using the overall OR from the published studies. No association was found for IL-1A gene for the risk of EARR. However, the dominant and co-dominant models of IL-1RN gene polymorphism were associated with the risk of EARR . Conclusion: More studies are warranted to determine the relationship between IL-1A and IL-1RN gene polymorphisms and EARR for a clearer understanding of their interactions.

Relationship Between Polymorphisms of Interleukin-1 Receptor Antagonist (IL-1Ra) Genes and Susceptibility to Systemic Lupus Erythematosus in Iranian Population.

Interleukin (IL)-1 has a major role in cell destruction and inflammation. IL-1 receptor antagonist (IL-1RN or IL-1Ra) is a natural anti-inflammatory molecule that blocks IL-1. We intended to determine whether IL-1RN or IL-1Ra variable number tandem repeat (VNTR) polymorphism is associated with susceptibility to systemic lupus erythematosus (SLE) in a series of patients in the Northeastern part of Iran. Genomic DNA was extracted from the whole blood of 104 SLE patients and 209 subjects without SLE as a control group. The control group was matched for age and gender with SLE patients. Then, genomic DNA was genotyped by polymerase chain reaction (PCR) method for a length polymorphism in intron 2 of the IL-1RN gene. Of five alleles, only allele 4 of IL-1RN had a higher frequency in healthy subjects (2.4%) compared to SLE patients (0), with a statistically significant difference (P= 0.03). Eleven kinds of polymorphisms of IL-1RN were found including 1/1, 1/2, 2/2, 3/3, 1/3, 3/5, 2/3, 2/5, 1/5, 4/4 and 1/4 in both groups. In genotype frequency, there was no statistically significant difference regarding gene polymorphism kinds between the two groups (P= 0.29). Alleles 4 of IL-1RN may have a protective role against SLE susceptibility. However, SLE was not associated with any of the 11 kinds of genotype IL1-RN gene polymorphisms studied here.

The relevance of IL-1β and IL-1RN gene polymorphisms in the etiology of preterm delivery in the population of Polish women.

Preterm delivery (PTD) is one of the important challenges for perinatal medicine due to prematurity and associated complications. The mechanisms leading to the PTD occurrence are not fully clarified and it is assumed that PTD is a complex phenomenon caused by many different pathophysiological factors. Nowadays, an important role is attributed to genetic determinants of PTD, pointing to possible relevance of polymorphic variants of candidate genes to participate in the etiology of PTD. The aim of the study was to assess the relevance of +3953C > T IL-1β and 86 bp VNTR IL-1RN gene polymorphisms in the etiology of PTD in Polish women. Study group consisted of 150 women (mean age 29.2 ± 5.6 years, mean weeks of gestational age 33.7 ± 2.8 gw.) with preterm delivery (22 + 0 - 36 + 6 gw.). To the control group 150 healthy pregnant women (mean age 29.0 ± 3.7 years, mean weeks of gestational age 39.3 ± 1.2 gw.) who delivered > 37 gw. were enrolled. All investigated polymorphisms were analyzed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). The interesting observation was the notice of overrepresentation of 2/2 genotype of IL-1RN gene in the control group (8.0 vs. 3.3%, p = 0.06) and 2 allele in the control group (25.0 vs. 20.0%, p = 0.07). The +3953C > T polymorphism of IL-1β gene probably is not connected with the risk of preterm delivery. The study results points to the possible modulating effect of mutated IL-1RN* 2 allele (86 bp VNTR polymorphism) of IL-1RN gene in decreased risk of preterm delivery.

Association of ENAM, TUFT1, MMP13, IL1B, IL10 and IL1RN gene polymorphism and dental caries susceptibility in Chinese children.

ObjectiveTo investigate the association between single nucleotide polymorphisms (SNPs) in six candidate genes (enamelin [ENAM]; tuftelin 1 [TUFT1]; matrix metallopeptidase 13 [MMP13]; interleukin 1 beta [IL1B]; interleukin 10 [IL10]; interleukin 1 receptor antagonist [IL1RN]) and dental caries in children from northwest China.MethodsThis case–control study enrolled children (12–15 years) who underwent routine dental examinations. The children were divided into two groups based on the presence of dental caries. A saliva sample was collected and seven SNPs (rs3806804A/G in ENAM, rs3811411T/G in TUFT1, rs2252070A/G and rs597315A/T in MMP13, rs1143627C/T in IL1B, rs1800872A/C in IL10 and rs956730G/A in IL1RN) were genotyped.ResultsA total of 357 children were enrolled in the study: 161 with dental caries and 196 without dental caries. No significant difference was found in the alleles and genotypes of five genes (ENAM, TUFT1, MMP13, IL10 and IL1RN) between those with and without dental caries. A significant relationship was found between the IL1B rs1143627C/T polymorphism and dental caries susceptibility with those carrying the rs1143627CT genotype having a lower risk of dental caries compared with those carrying the CC genotype (odds ratio 0.557; 95% confidence interval 0.326, 0.952).ConclusionThe IL1B rs1143627C/T polymorphism may be associated with dental caries susceptibility in children from northwest China.

Association of IL-1β, IL-1RN, and ESR1 genes polymorphism with risk of infection and response to sofosbuvir plus daclatasvir combination therapy in hepatitis C virus genotype-4 patients.

Sofosbuvir (SOF) and daclatasvir combination with or without ribavirin proved to be effective and safe in the treatment of hepatitis C virus infection. The study aimed to assess the efficacy of (SOF plus daclatasvir) combination + ribavirin in the treatment of treatment-experienced HCV genotype 4 Egyptian patients and to investigate the impact of IL-1β _31, IL-1β _511, and IL-1RN and T29C of ESR1 genes polymorphisms on treatment outcome. The study also aimed to assess the effect of the treatment on liver fibrosis. The sustained virologic response was assessed at 0, 4, 12, and 24 weeks from the beginning of treatment by RT-PCR. IL-1β _31, IL-1β _511, IL-1RN, and T29C genes polymorphisms were examined by PCR-based techniques in two groups of patients (responders and non-responders) and a control group of healthy subjects. A significant association between IL-1β_511 gene polymorphism and SOF/DAV-induced response was observed, where the "CC" genotype was the most frequent in responders while the "CT" genotype was the most frequent among non-responders (P = 0.0001, OR = 39; 95% CI = 4.7-316). IL-1RN gene polymorphism also showed significant associations with response to treatment, genotypes that include allele "1" were the most frequent in responders, particularly the homozygous genotype "1/1" (P = 0.0001, OR = 2.3; 95% CI = 1.57-3.2). However, the genotypes "4/4" and "2/4" were the most frequent in non-responders; (P = 0.0001). At least 71% of the responders carry allele "1" while 54% of non-responders were allele "4" carriers (P value = 0.0001. OR = 2.8; 95% CI = 6.4-134.2). Liver fibrosis is significantly improved regardless of the response. © 2018 IUBMB Life, 70(11):1156-1163, 2018.

Association between cytokine gene polymorphisms and squamous cell lung cancer depending on the duration of smoking in men

Background. Squamous cell lung cancer (SCLC) is the most common form of lung cancer among men smokers. Mediators and products of inflammation can contribute to the initiation of carcinogenesis in smokers. The aim of study is to investigate the association between IL1B(rs1143634, rs16944), IL1RN (rs2234663), TNFA (rs1800629), IL6 (rs1800795), IL10 (rs1800896) genes and SCLC depending on the duration of smoking in men.
 Materials and methods. We studied 324 patients with SCLC and 168 healthy men smokers. The typing of the IL1RN(rs2234663) gene polymorphism has analyzed by polymerase chain reaction (PCR). Detection of the IL1B (rs1143634) and IL6 (rs1800795) polymorphisms have performed by restriction fragment length analysis, as a restriction enzyme TaqI was used. The IL1B (rs16944), TNFA(rs1800629) and IL10 (rs1800896) genes polymorphisms have determined through TaqMan-real-time PCR.
 Results. The study showed, the age, duration of smoking and the number of cigarettes smoked per day were the main risk factors for SCLC in men (p 0.0001). The IL6 -174G allele was detected an additional risk factor of SCLC at a smoking duration of less than 35 years (OR = 1.68; 95 % CI: 1.12-2.51; pcor = 0,04). No association of IL1B (rs1143634, rs16944), IL1RN (rs2234663), TNFA (rs1800629), and IL10 (rs1800896) genes with the risk of SCLC in men was identified.
 Conclusion. The duration of smoking and rs1800795 IL6 gene polymorphism may influence on the susceptibility to SCLC in men. Our results can be useful in understanding the molecular mechanisms of development of SCLC.

IL1RN gene polymorphism in a Portuguese population with implant-supported overdentures – An observational study

ObjectivesThis study aimed to evaluate the frequency of the different alleles of the VNTR IL1RN gene (86bp RP, intron 2), in a Portuguese Caucasian population with implant-supported overdentures. MethodsFifty-eight Caucasians rehabilitated with implant overdentures for at least 6 months, were randomly recruited from the Removable Prostheses Forms used in Faculty of Dental Medicine, University of Porto. After clinical examination, DNA was obtained through oral mucosa swab. PCR was used to identify the IL1RN gene alleles. The frequency estimates and the corresponding 95% CI for alleles and genotypes of the IL1RN gene were calculated using the exact binomial test. ResultsThe population included 44 females and 14 males. Only 2 subjects were smokers; 6 subjects had diabetes and 5 had chronic gastritis. The most frequent allele of IL1RN gene was allele 5, with an estimated frequency of 58.6%, followed by the allele 4 with a frequency of 48.3%. The alleles 1 and 2 were not detected. The most frequent genotype was allele 5/allele 5, followed by the allele 4/allele 4. ConclusionsAllele 5 was the most frequent IL1RN allele and allele 5/allele 5 was the most frequent genotype. Further studies are required in order to understand the role of alleles 5 and 4, as well as of the allelic combinations of the IL1RN gene polymorphism, on the development of biological complications with dental implants.

The role of interleukin-1 gene polymorphisms and Helicobacter pylori in gastroesophageal reflux disease.

Our aim is to assess the relationship between interleukin 1β (IL-1 β), (-511,-31 alleles), interleukin 1RN (IL-RN), Helicobacter pylori (HP) status and gastroesophageal reflux disease (GERD) diagnosed by pH monitoring in the Turkish population. A Total of 100 consecutive patients with GERD were enrolled in the study. Genotypes of IL-1β (-511,-31), IL-1RN gene polymorphisms and HP status of the patients were analyzed. While thirty-two patients were diagnosed as esophagitis with varying severity the remaining patients had no esophagitis. Seventy six participants were positive for HP and the remaining patients were negative. The difference between erosive and non-erosive groups was statistically significant when we compared IL-1β (-511) but no difference regarding IL-1β (-31) and IL-1RN variations. We also analyzed T/T, C/T and C/C alleles and the difference was significant statistically in T/T allele between patients with and without erosive GERD 1 (3.1%) vs. 12 (17.9%), respectively with a p value<0.05. But C/C, C/T alleles of (-511), (-31) and IL-1RN polymorphisms were not statistically significant between the groups. IL-1β genetic polymorphisms may take part in the pathophysiology of gastroesophageal reflux disease.

The IL-1RN and IL-4 gene polymorphisms are potential genetic markers of susceptibility to bladder cancer: a case-control study.

We investigated the relationship between the distribution of the IL-1RN, TNF-β and IL-4 polymorphism and the clinical features of bladder cancer. A total of 100 patients with bladder carcinoma and 102 healthy control subjects were enrolled in the study. The IL-1RN, IL-4 and TNF-β gene polymorphisms were identified by PCR restriction fragment length polymorphism-based analysis. Allelic frequencies were compared between patient and the controls. Tumor stage, histopathological grade, tumor size/number and smoking condition were evaluated with IL-1RN, IL-4 and TNF-β gene polymorphisms. Allele distribution frequencies of IL-1RN and IL-4 gene polymorphisms were significantly different between patients and control groups. However, allele distribution of TNF-β gene was not statistically significant. There was no difference in allele distribution of the three genes in both groups regarding stage, tumor size, number of tumors and smoking condition. Although allele distribution of IL-4 gene showed significant difference considering histopathological grades in both smoking and total patients group, allele distribution of IL-1RN and TNF-β was not different. The present research suggests that the IL-1RN and IL-4 gene polymorphisms are potential genetic markers of susceptibility to bladder cancer. In the future, clinical improvements on diagnosis, treatment and prognosis of bladder carcinoma are expected owing to development of more sensitive and specific tests for genetic polymorphisms of cytokines that are effective on inflammation.

Gene polymorphisms and febrile neutropenia in acute leukemia--no association with IL-4, CCR-5, IL-1RA, but the MBL-2, ACE, and TLR-4 are associated with the disease in Turkish patients: a preliminary study.

The aim of this study was to investigate the mannose-binding lectin 2 (MBL-2), interleukin (IL)-4, Toll-like receptor 4 (TLR-4), angiotensin converting enzyme (ACE), chemokine receptor 5 (CCR-5), and IL-1 receptor antagonist (RA) gene polymorphisms (GPs) in acute leukemias (ALs) and to evaluate their roles in febrile neutropenia (FN) resulting from chemotherapy. The study included 60 AL patients hospitalized between the period of July 2001 and August 2006. Polymorphisms for the genes ACE(I/D), CCR-5, IL-1RA, MBL-2, TLR-4, and IL-4 were typed by polymerase chain reaction (PCR) and/or PCR-restriction fragment length polymerase. Genotype frequencies for these genes were compared in the patient and control groups. The relationships between the genotypes and the body distribution of infections, pathogens, the duration of neutropenia, and febrile episodes in AL patients were evaluated. No significant differences in either the genotype distribution or the allelic frequencies of TLR-4, IL-4, CCR-5, IL-1RN GPs were observed between patients and healthy controls. The AB/BB genotype (53.3%) in the MBL-2 gene was found to be significantly higher in the AL patients compared with control groups. There were correlations between the presence of MBL-2, TLR-4, and ACE polymorphisms and clinical parameters due to FN. Overall, bacteremia was more common in MBL BB and ACE DD. Gram-positive bacteremia was more common in ACE for ID versus DD genotype. Gram-negative bacteremia was more common for both the MBL-2 AB/BB genotype and TLR-4 AG genotype. Median durations of febrile episodes were significantly shorter in ACE DD and MBL AB/BB. Although TLR-4, ACE, and MBL-2 GPs have been extensively investigated in different clinical pictures, this is the first study to evaluate the role of these polymorphisms in the genetic etiopathogenesis of FN in patients with ALs. As a conclusion, TLR-4, ACE, and MBL-2 genes might play roles in the genetic etiopathogenesis of FN in patients with ALs.

A possible role of IL-1RN gene polymorphism in the outcome of gastrointestinal diseases associated with H. pylori infection

ObjectiveTo verify whether the variable number of tandem repeat (VNTR) polymorphism in the IL-1RN gene that encodes the interleukin (IL)-1 receptor antagonist (IL-1Ra) plays a role in the outcome of gastrointestinal diseases associated with Helicobacter pylori (H. pylori) infection.MethodsPatients with normal endoscopy (n = 71), inflammation of the upper gastrointestinal tract only (n = 196), gastric ulcer (n = 28), duodenal ulcer (n = 76), and gastric cancer (n = 19) were studied. H. pylori infection was diagnosed by the urease test, histological examination, and polymerase chain reaction. The IL-1 receptor antagonist gene (IL-1RN intron 2 VNTR) was analyzed by polymerase chain reaction. Gastritis was scored according to the updated Sydney system of classification.ResultsH. pylori infection was an independent risk factor for mild (odds ratio [OR] = 5.53 [95% confidence interval [CI] = 2.63–11.64; P < 0.05]), moderate (OR = 83.93 [95% CI = 29.7–237.18; P < 0.05]) and marked (OR = 47.47 [95% CI = 5.39–418.05; P < 0.05]) gastritis. The carriage of IL-1RN*2/*2 had a significant protective effect of H. pylori infection (OR = 0.31 [95% CI = 0.17–0.57; P < 0.05]). H. pylori infection was identified as an independent risk of inflammation, duodenal ulcer, and gastric ulcer. The carriage of IL-1RN*2/*2 was an independent risk factor for gastric cancer (OR = 5.81 [95% CI = 1.06–31.98; P < 0.05]); nonetheless, the carriage of allele 2 (IL-1RN*2/*2 plus IL-1RN*L/*2) had an independent protective effect on duodenal ulcer (OR = 0.45 [95% CI = 0.22–0.91; P < 0.05]).ConclusionsAllele 2 of the VNTR IL-1RN polymorphism had a protective effect against duodenal ulcer and H. pylori infection; however, it increased the risk of gastric cancer.

The Interleukin-1 Gene Cluster Polymorphisms Are Associated with Takayasu's Arteritis in Mexican Patients

Takayasu's arteritis (TA) is a chronic inflammatory arteritis of unknown etiology involving mainly the aorta and its major branches. The interleukin (IL) 1β and IL-1 receptor antagonist have been playing an important role as regulators of inflammation. We investigated whether the polymorphisms at the IL-1B and IL-1RN gene cluster were associated with the genetic susceptibility to develop TA. We analyzed the IL-1B, IL-1F10.3, and IL-1RN polymorphisms in a sample of 58 TA patients, and 248 clinically healthy unrelated Mexican individuals by 5' exonuclease TaqMan polymerase chain reaction. Polymorphic haplotypes were constructed after linkage disequilibrium analysis. We found increased frequencies of different polymorphisms (C allele and TC genotype of IL-1F10.3; TT genotype of IL-1RN.4; C allele and TC genotype of IL-1RN6.1; G allele of IL-1RN6.2 and haplotypes "1T" and "1C" of IL-RN VNTR and IL-1RN6.1) in the group of TA when compared to healthy controls. On the other hand, decreased frequency of IL-1-511 TC genotype was found in the TA group compared to controls. IL-1B and IL-1RN gene polymorphisms could be involved in the risk of developing TA in the Mexican population. These associations were independent of the affected vessels.

Distribution of theIL-1RN,IL-6,IL-10,INF-γ, andTNF-αGene Polymorphisms in the Mexican Population

Cytokines are a group of polypeptides with an important role in the inflammatory response. It has been suggested that certain polymorphisms located in several cytokine genes are associated with different diseases. The aim of the present study was to establish the gene frequency of 13 polymorphisms of the IL-1RN, IL-6, IL-10, INF-γ, and TNF-α genes in a Mexican population. These polymorphisms have been reported in several populations, with important variation in frequency according to the studied population. Thirteen polymorphisms (rs419598, rs315951, rs2234663, rs3811058, rs1800796, rs2069827, rs1800896, rs1800871, rs1800872, rs1800629, rs2069709, rs2069710, and rs361525) were analyzed by 5' exonuclease TaqMan genotyping assays in a group of 248 healthy unrelated Mexican individuals. The results obtained showed that the studied Mexican population presents significant differences (p<0.05) in the distribution of the IL1RN (rs419598, rs315951, and and rs2234663), IL1F10 (rs3811058), IL6 (rs1800796, rs2069827), IL10 (rs1800896, rs1800871, and rs1800872), and TNF-α (rs1800629) polymorphisms when compared to Caucasian, Asian, and African populations. In summary, the distribution of the IL-1RN, IL-6, IL-10, and TNF-α cytokine gene polymorphisms distinguishes the studied Mexican population from other groups. Since the alleles of these cytokines are associated with the development of several inflammatory diseases, knowledge of the distribution of these alleles in the studied Mexican population could be helpful to understand their true role as a genetic susceptibility marker in this population.

353 The Vntr Il1Rn Gene Polymorphism in Polish Children with Diffuse Mesangial Proliferation (DMP)

Pathogenesis of several renal diseases is strongly connected with cytokines. The polymorphism of IL1RN gene exists in intron 2 and is caused by variable number of 86bp sequence repeats. In addition, previous studies confirmed the association of IL1RN*2 with inflammatory diseases, among them glomerulonephritis. Therefore it raises the question whether VNTR polymorphism of IL1RN gene determines the susceptibility to DMP and its clinical course.The study group consisted of 56 children with DMP and 105 healthy children as controls. Genomic DNA was extracted from peripheral blood leukocytes. The IL1RN intron 2 VNTR polymorphism was determined by PCR technique with primers flanking the polymorphic region. Significant differences in genotype (p=0,032) and allele (p=0,045) frequencies were observed between children with DMP and control group. The genotype distribution was as follows: *1/*1 - 48,2%, *1/*2 - 30,4%, *1/*3 - 3,6%, *2/*2 - 14,3%, *3/*3 - 1,8%, *3/*4 - 1,8% in DMP group and *1/*1 - 58,1%, *1/*2 - 36,2%, *1/*3 - 3,8%, *2/*2 - 1,9% in controls. The prevalence of alleles in children with DMP was: *1 - 65,2%, *2 - 29,4%, *3 - 4,5%, *4 - 1,9% while in control group: *1 - 78,1%, *2 - 20%, *3 -1,9%. Additionally IL1RN*2 allele homozygosity showed eight fold higher risk for DMP (OR=8,58; 95%CI, 1,73 to 42,48; p=0,008). No association between IL1RN genotypes and response to steroid therapy or frequency of relapses was observed in the study group.Our results suggest that IL1RN*2 homozygosity predisposes to diffuse mesangial proliferation in Polish children.

Association of IL1B and IL1RN gene polymorphisms with the predisposition to hemorrhagic fever with renal syndrome and with the specific features of its course

-511C > T and 3953C > T polymorphic loci of the IL1B gene and VNTR polymorphism in the second intron of the IL1RN gene were analyzed in 335 patients with hemorrhagic fever with renal syndrome (HFRS) and 300 seronegative donors. As compared with the controls, the patients with HFRS were significantly less frequently found to have IL1RN*I/*II genotype (p = 0.03; OR = 0.69; 95% CI 0.49-0.96) and combinations of I/II-C/T-C/C and I/II-C/ T-C/T (IL1RN*VNTR - IL1B*-511C > T - IL1B*395C > T) genotypes (p = 0.03; OR = 0.58; 95%CI 0.36-0.95 and (p = 0.008; OR = 0.53; 95% CI 0.32-0.87, respectively). IL1B*C/*T genotype at the locus -511C > T of the IL1B gene (p = 0.04; OR = 1.77; 95% CI 1.02-3.09) and combinations of C/T-I/I (IL1B*-511C > T - IL1RN*VNTR) genotypes were predominant in patients with severe HFRS (p = 0.002; OR = 2.44; 95% CI 1.38-4.29). Furthermore, the carriers of IL1B*C/*T genotype at the locus -511C > T of the IL1B gene and combinations of C/T-I/I (IL1B*-511C > T - IL1RN*VNTR) genotypes were at higher risk for infectious-toxic shock (p = 0.03; OR = 2.78; 95% CI 1.10-7.38 and (p = 0.02; OR = 2.67; 95%CI 1.15-6.13, respectively). The likelihood of disseminated intravascular coagulation was higher in individuals with a combination of T/T-C/T genotypes at the polymorphic loci -511C > T, 3953C > T of the IL1B gene (p = 0.009; OR = 6.4; 95% CI 1.45-21.3). The performed study confirms the assumption that the polymorphisms of -511C > T and 3953C > T of the IL1B and VNTR polymorphism of IL1RN gene has impact on predisposition to HFRS and the pattern of its course.

Associations of the IL‐1 and TNF gene polymorphisms in the susceptibility to duodenal ulcer disease in Chinese Han population

Our aim was to investigate whether genetic polymorphism of IL-1Beta-511, IL-1RN, TNF-A-308 are involved in the susceptibility to duodenal ulcer (DU). 437 unrelated Chinese Han patients with DU and 148 healthy controls were genotyped by the polymerase chain reaction-restriction fragment length polymorphism method for the IL-1B-511, TNF-A-308 gene polymorphisms and the VNTR polymorphism in intron 2 of the IL-1RN gene polymorphisms. There was no difference in the genetic polymorphism of IL-1Beta-511, IL-1RN and TNF-A-308 in the patients with DU compared with control. After stratified by Helicobacter pylori infection, they also could not reach significant differences in this study. No statistically significant differences were observed in DU group compared with control according to combination of the IL-1Beta-511 and IL-1RN genotypes regardless of H. pylori positivity. These findings show that no evidence for the involvement of a proinflammatory polymorphism in the IL-1Beta-511, IL-1RN and TNF-A-308 in the susceptibility to DU in China.

Relevance of IL-1 and TNF gene polymorphisms on interleukin-1β and tumor necrosis factor-α gastric mucosal production

We aimed to evaluate the influence of Helicobacter pylori infection and IL-1/TNF gene polymorphisms on interleukin (IL)-1β and tumor necrosis factor (TNF)-α gastric mucosal production. IL-1β and TNF-α levels in homogenized biopsy specimens taken from the antrum and corpus of 81 patients were measured by enzyme-linked immunosorbent assay. Genomic DNA was typed for the IL1B-511, IL1B+3954, variable number of tandem repeat (VNTR) IL1RN, TNFA-308, TNFA-238, LTA NcoI, and LTA Bsi gene polymorphisms by polymerase chain reaction, restriction fragment length polymorphism, and TaqMan assays. H. pylori infection and CagA/VacA antibody status were determined by Western blot. IL-1β and TNF-α protein levels were significantly higher in the gastric antrum of patients infected with H. pylori compared with uninfected patients [9.54 (5.07–16.28) vs. 4.55 (3.69–8.28) pg IL-1β/mg protein, p = 0.004, and 1.5 (0.7–2.71) vs. 0.63 (0.3–1.26) pg TNF-α/mg protein, p = 0.001]. Among H. pylori-infected individuals, carriers of the IL1RN*2 allele had significantly higher antrum mucosal IL-1β levels than noncarriers [15.97 (9.59–26.6) vs. 10.08 (7.72–13.33), p = 0.008]. No association between gastric mucosal TNF-α levels and genotypes of the TNFA and LTA gene polymorphisms was reported. Our results indicate that the VNTR polymorphism of the IL1RN gene influences IL-1β gastric mucosal production in patients infected with H. pylori.

Interleukin-1 and TNF-α polymorphisms and Helicobacter pylori in a Brazilian Amazon population

To study the association between Interleukin-1 (IL-1) and tumor necrosis factor (TNF)-alpha polymorphisms, infection by Helicobacter pylori (H pylori) and the development of gastrointestinal diseases. Genomic DNA was extracted from the peripheral blood of 177 patients with various gastrointestinal diseases and from 100 healthy volunteers. The polymorphisms in IL-1beta and TNF-alpha genes were analyzed using the polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP) and those from IL-1RN with PCR. The presence of infection due to H pylori and the presence of the CagA toxin were detected by serology. The histopathological parameters in the gastric biopsies of the patients were according to the Sydney classification. A comparison of the frequencies of the different polymorphisms studied among the patients and the control group demonstrated that the allele IL-1RN*2 was more frequent among patients with gastric ulcers and adenocarcinoma. Carriers of the allele IL-RN*2 and those with reactive serology for anti-CagA IgG had a greater risk of developing peptic ulcer and gastric adenocarcinoma, as well as a higher degree of inflammation and neutrophilic activity in the gastric mucosa. Our results indicate a positive association between IL-1RN gene polymorphism and infection by positive H pylori CagA strains and the development of gastric ulcers and adenocarcinoma.