Interleukin-1 Beta Polymorphisms Research Articles

Effect of genetic polymorphisms of interleukin-1 beta on the microscopic portal vein invasion and prognosis of hepatocellular carcinoma.

Several studies have demonstrated a relationship between genetic polymorphisms of interleukin-1 beta (IL-1β) and cancer development; however, their influence on cancer prognosis is unknown. In the present study, we aimed to evaluate the impact of IL-1β single nucleotide polymorphisms on the hematogenous dissemination and prognosis of hepatocellular carcinoma. We conducted a retrospective cohort study including patients with hepatocellular carcinoma who underwent primary liver resection at our hospital between April 2015 and December 2018. The primary endpoints were overall and recurrence-free survival. Secondary endpoints were microscopic portal vein invasion and number of circulating tumor cells. A total of 148 patients were included, 32 with rs16944 A/A genotype. A/A genotype was associated with microscopic portal vein invasion and number of circulating tumor cells (p = .03 and .04). In multivariate analysis, A/A genotype, alpha-fetoprotein level, and number of circulating tumor cells were associated with microscopic portal vein invasion (p = .01, .01, and <.01). A/A genotype, Child-Pugh B, and intraoperative blood loss were independent predictive factors for overall survival (p = .02, <.01, and <.01). Our results indicate that the IL-1β rs16944 A/A genotype is involved in number of circulating tumor cells, microscopic portal vein invasion, and prognosis in HCC.

Association Between the Polymorphism of Angiotensin-Converting Enzyme Gene and Interleukin-1 Beta Gene and the Response to Erythropoietin Therapy in Dialysis Patients with Anemia.

The polymorphism of the angiotensin-converting enzyme (ACE) gene and interleukin-1 beta (IL-1b) gene could be associated with resistance in the treatment of anemia in dialysis patients with recombinant human erythropoietin (rHuEPO). The aim of the study was to evaluate the association between the polymorphism of the ACE and IL-1b genes and the response to rHuEPO therapy in dialysis patients with anemia. The study investigated 69 patients on dialysis with anemia treated with recombinant human erythropoietin for 12 months. Genotyping of ACE and IL-1b polymorphism was done in all study patients at the initiation of the study. The patient's demographic characteristics, dialysis vintage, and laboratory parameters were also evaluated as factors associated with rHuEPO resistance. The erythropoietin resistance index (ERI) was calculated as the weekly rHuEPO dose per kg of body weight, divided by the hemoglobin (Hb) concentration in g/dl. The Hb ≥ 110 g/l was registered in 37 (53.6%) patients. Patients with Hb ≥ 110 g/l were characterized by significantly higher serum levels of albumin, cholesterol, and iron than those with Hb < 110 g/l. The serum level of the CRP, the weekly dose of rHuEPO, and ERI were significantly higher in patients with Hb < 110 g/l compared to patients with Hb ≥ 110 g/l. The ERI value of ≥ 10 IUkg/weekly/g/dl was present in 27 (39.1%) patients. The serum levels of ferritin and CRP, and weekly dose of rHuEPO were significantly higher in patients with ERI value ≥ 10 IU kg/weekly/g/dl compared with the patients with ERI value < 10 IUkg/weekly/g/dl. There was no significant association between the ERI and polymorphism of the ACE and IL-1b genes in study patients. The polymorphism of the ACE and IL-1b genes was not significantly associated with the response to erythropoietin therapy in dialysis patients with anemia. Iron deficiency, malnutrition, and inflammation were factors associated with anemia and resistance to erythropoietin therapy in dialysis patients.

A preliminary study on the association between pro-inflammatory cytokine IL-1 beta polymorphisms and susceptibility to hepatitis C infection in Malay male Malay drug abusers

Introduction: Hepatitis C virus (HCV) infection frequently leads to liver complications, such as fibrosis, cirrhosis, and hepatocellular carcinoma. The incidence of HCV infection transmission among drug abusers is concerning. Interleukin-1 beta (IL-1b) is a pro-inflammatory cytokine secreted during innate and adaptive immune responses and plays a pivotal role in chronic inflammatory diseases. Functional single nucleotide polymorphisms in IL-1b cause it to play different roles in disease susceptibility and progression. This study aimed to investigate the association between genetic polymorphisms of pro-inflammatory cytokines (IL-1b) and HCV infection susceptibility in Malay male drug abusers. Methods: In total, 48 male Malay drug abusers were included in this retrospective case-control study. Genomic DNA was extracted from whole blood samples and analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for the IL-1b rs16944 and rs1143634 polymorphisms. Results: Analysis of IL-1b rs1143634 revealed that the C/C genotype was common in both the case and control groups; however, no statistical significance was observed (p = 0.068, c2 = 3.755). Genotyping of IL-1b demonstrated that all samples were of the homozygous mutant type (T/T). Conclusion: There was no association between IL-1b polymorphism (rs1143634 and rs16944) and hepatitis C infection susceptibility among Malay male drug abusers.

Hashimoto thyroiditis in Lebanon: Fibrinogen levels increase and redox homeostasis alteration in euthyroid patients and detection of a new SAA1 “ε” isoform (V52-V57)

Hashimoto's thyroiditis (HT), the most common cause of hypothyroidism, is a multifactorial autoimmune condition characterized by elevated levels of anti-thyroid peroxidase (anti-TPO) and/or anti-thyroglobulin (anti-Tg), and involving both environmental and genetic factors. This study was designed to evaluate the levels of acute phase reactants and the oxidant/antioxidant status among Lebanese HT patients. It also aims to assess the possible association between selected polymorphisms of three genes, Serum amyloid A1 (SAA1), Interleukin 1 beta (IL1B) and Interleukin 1 receptor antagonist (IL1RN), and the occurrence of the disease. The study included 21 patients diagnosed with HT and 22 healthy controls. Fibrinogen, SAA, mannose binging lectin (MBL), C-reactive protein (CRP) and IL1B levels were analyzed by enzyme-linked immunosorbent assay (ELISA). The lipid peroxidation marker malondialdehyde (MDA) and the antioxidant enzyme catalase were assessed using assay kits. SAA1 (+2995C>T and +3010C>T) and IL1B polymorphisms (g. –511C>T, g. –31T>C and g. +3954C>T) were assessed by polymerase chain reaction (PCR)-digestion. The IL1RN 86 bp variable number of tandem repeats (VNTR) was identified by fragment-size analysis. Fibrinogen levels were significantly higher in HT patients than controls (p < 0.0001), unlike other inflammatory markers which showed comparable levels between both groups. IL1B levels were not detected in plasma of patients and controls. An increase in MDA levels (p < 0.0001) coupled with a decrease in catalase activity (p = 0.034) were observed in the patients' group as compared to controls. No significant association was found between the alleles and genotypes of the studied polymorphisms and the occurrence of the disease. Interestingly, a new SAA1 allele, assigned as “ε”, was observed in two Lebanese HT patients. Our results suggest an ongoing subclinical inflammation and an alteration of the redox homeostasis in HT patients.

Influence of genetic variations in IL1B on brain region volumes in bipolar patients and controls

Involvement of the immune system has been implicated in the etiology and pathophysiology of mood disorders, including bipolar disorder. Neuroimaging studies have reported structural brain pathology in bipolar disorder patients, and both levels of and genetic variants in cytokines have been associated with altered volumes of brain regions. The aim of this study was to investigate associations between single nucleotide polymorphisms in the gene coding for the pro-inflammatory cytokine interleukin-1 beta (IL1B) and whole brain grey matter volume, as well as volumes of several brain regions shown to be of importance in mood disorders. Structural magnetic resonance imaging and vertex-based morphometry were used to obtain volume of different brain regions in subjects with bipolar disorder (n=188) and healthy controls (n=54). Four IL1B polymorphisms were genotyped: rs1143623, rs1143627, and rs16944 in the promoter region together with the synonymous variant rs1143634 in the IL1B gene. The genotype distribution did not differ between bipolar subjects and controls. The T allele at rs16944 and the C allele at rs1143627 were associated with increased volumes of the putamen of the left hemisphere in patients and controls, which lends support to the role of this immune system mediator for brain structure.

Association of Neuropeptide-Y (NPY) and Interleukin-1beta (IL1B), Genotype-Phenotype Correlation and Plasma Lipids with Type-II Diabetes.

BackgroundNeuropeptide Y (NPY) is known to play a role in the regulation of satiety, energy balance, body weight, and insulin release. Interleukin-1beta (IL1B) has been associated with loss of beta-cell mass in type-II diabetes (TIID).ObjectivesThe present study attempts to investigate the association of NPY exon2 +1128 T/C (Leu7Pro; rs16139), NPY promoter -399 T/C (rs16147) and IL1B -511 C/T (rs16944) polymorphisms with TIID and their correlation with plasma lipid levels, BMI, and IL1B transcript levels.MethodsPCR-RFLP was used for genotyping these polymorphisms in a case-control study involving 558 TIID patients and 1085 healthy age-matched controls from Gujarat. Linkage disequilibrium and haplotype analysis of the NPY polymorphic sites were performed to assess their association with TIID. IL1B transcript levels in PBMCs were also assessed in 108 controls and 101 patients using real-time PCR.ResultsOur results show significant association of both structural and promoter polymorphisms of NPY (p<0.0001 and p<0.0001 respectively) in patients with TIID. However, the IL1B C/T polymorphism did not show any association (p = 0.3797) with TIID patients. Haplotype analysis revealed more frequent association of CC and CT haplotypes (p = 3.34 x 10−5, p = 6.04 x 10−9) in diabetics compared to controls and increased the risk of diabetes by 3.02 and 2.088 respectively. Transcript levels of IL1B were significantly higher (p<0.0001) in patients as compared to controls. Genotype-phenotype correlation of IL1B polymorphism did not show any association with its higher transcript levels. In addition, NPY +1128 T/C polymorphism was found to be associated with increased plasma LDL levels (p = 0.01).ConclusionThe present study provides an evidence for a strong correlation between structural and promoter polymorphisms of NPY gene and upregulation of IL1B transcript levels with susceptibility to TIID and altering the lipid metabolism in Gujarat population.

Interactions between environmental factors and maternal–fetal genetic variations: strategies to elucidate risks of preterm birth

ContextPreterm birth (PTB) is a complex disease in which medical, social, cultural, and hereditary factors contribute to the pathogenesis of this adverse event. Interactions between genes and environmental factors may complicate our understanding of the relative influence of both effects on PTB. To overcome this, we combined data obtained from a cohort of newborns and their mothers with multiplex analysis of inflammatory-related genes and several environmental risk factors of PTB to describe the environmental–genetic influence on PTB. ObjectiveThe study aimed to investigate the association between maternal and fetal genetic variations in genes related to the inflammation pathway with PTB and to assess the interaction between environmental factors with these variations. Study designWe conducted a case–control study at the Pereira Rossell Hospital Center, Montevideo, Uruguay. The study included 143 mother–offspring dyads who delivered at preterm (gestational age<37 weeks) and 108 mother–offspring dyads who delivered at term. We used real-time PCR followed by a high-resolution melting analysis to simultaneously identify gene variations involved in inflammatory pathways in the context of environmental variables. The genes analyzed were: Toll-like receptor 4 (TLR4), Interleukin 6 (IL6), Interleukin 1 beta (IL1B) and Interleukin 12 receptor beta (IL12RB). ResultsWe detected a significant interaction between IL1B rs16944 polymorphism in maternal samples and IL6 rs1800795 polymorphism in newborns, emphasizing the role of the interaction of maternal and fetal genomes in PTB. In addition, smoke exposure and premature rupture of membranes (PROM) were significantly different between the premature group and controls. IL1B and IL6 polymorphisms in mothers were significantly associated with PTB when controlling for smoke exposure. TLR4 polymorphism and PROM were significantly associated with PTB when controlling for PROM, but only in the case of severe PTB. ConclusionsInteractions between maternal and fetal genomes may influence the timing of birth. By incorporating environmental data, we revealed genetic associations with PTB, a finding not found when we analyzed genetic data alone. Our results stress the importance of studying the effect of genotype interactions between mothers and children in the context of environmental factors because they substantially contribute to phenotype variability.

EVALUATION OF INTERLEUKIN-6, LYMPHOTOXIN-α AND TNF-α GENE POLYMORPHISMS IN CHRONIC PERIODONTITIS

Background: Periodontitis is a chronic inflammatory disruption of the periodontal supportive tissues. There are the numerous evidences for his bacterial etiology. Though the occurrence of periodontal bacteria is considered to be the main cause of periodontitis, certain characteristics of the individual immune response may also have inuuence on the disease development and progression, and on the treatment outcomes. There are some reports that attempt to identify genetic factors associated with periodontitis including polymorphisms of interleukin-1 beta (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) genes. We were interested from the distribution of several genotypes of the cytokines: interleukin-6 (G-174C) and (G-597A), lymphotoxin-α (A+252G), and tumour necrosis factor-alpha (G-308A) in patients with chronic periodontitis. Aim: To investigate the association of chronic periodontitis with certain gene polymorphisms of interleukin-6 (IL-6), Lymphotoxinα, and tumor necrosis factor-alpha (TNF-α). Material and methods: The study included 30 patients with moderate or severe chronic periodontitis, and 10 persons with healthy periodontium. Total genomic DNA was extracted from the buccal epithelial cells. TNF-A (G-308A), IL-6 (G-174C), IL-6 (G-597A) and LT-A (A+252G) genes polymorphisms were analyzed by Polymerase chain reaction (PCR). Results: Outcomes showed a large variety in genotype’s distribution in the investigated groups. No important difference was observed in the distribution of IL-6, TNF-α and LT-α genotypes between chronic periodontitis patients and controls in this study be reason of the small studied group. However, a signiucant difference in the LT-α was observed – a prevalence of the genotype GG in patients with severe periodontitis. In relation with IL-6 (G-597A) and IL6 (G-174C) genotyping in both of them in patients with severe periodontitis was occurred most frequently the genotype GG. In patients with periodontitis the frequency of genotype GG of TNF-α (G-308A) was significantly increased. Conclusion: The assessment IL-6 (G-597A) and IL6 (G-174C), and TNF-α (G-308A) revealed that genotype GG was moderate associated with chronic periodontitis in Bulgarian individuals. As a result of these findings we may suppose that the G allele may play an important role in the development and progression of periodontal disease in this population. The frequency of LT-A (A252G) was significantly greater in severe periodontitis patients in this study.

Association of Interleukin-1 Gene Single Nucleotide Polymorphisms with Keratoconus in Chinese Han Population

ABSTRACTPurpose: To investigate whether interleukin-1 alpha (IL1A) and interleukin-1 beta (IL1B) polymorphisms are associated with keratoconus (KC) in unrelated Chinese Han patients.Methods: The IL1A (rs2071376) and IL1B (rs1143627, rs16944) polymorphisms were genotyped in 115 unrelated Chinese Han KC patients and 101 healthy Chinese Han volunteers with the Sequenom MassARRAY RS1000. Sequenom Typer 4.0 software, PLINK 1.07, Haploview 4.0 software platform were used to analyze the allelic variants of IL1A and IL1B genes, and their association with KC risk factors were assessed.Results: Among the variants, the three SNPs (rs2071376 in IL1A, rs1143627 and rs16944 in the promoter region of IL1B) were different between the two groups. The A allele of rs2071376 (A > C, p = 0.017, OR = 1.968, 95% C.I. 1.313–3.425), the C allele of rs1143627 (C > T, p < 0.001, OR = 2.864, 95% C.I. 1.631–4.968) and the A allele of rs16944 (A > G, p = 0.002, OR = 2.401, 95% C.I. 1.396–4.161) were associated with a increased risk of KC in Chinese Han patients. This study showed that rs2071376, rs1143627 and rs16944 had significant differences in associations between KC patients and the control group when different genotypes were analyzed in three models (dominant, recessive, and additive). In the haplotype analysis, the two single nucleotide polymorphisms (SNPs), rs1143627 and rs16944 showed strong linkage disequilibrium. In addition, Haplotype “ACA” was found to be associated with a higher risk of developing KC (OR = 12.91, p < 0.001).Conclusion: Keratocyte apoptosis is an initiating event in the pathogenesis of KC which could be induced by the altered levels of IL1 gene. These findings confirmed that polymorphisms in IL1 genes were associated with risk of KC in the Chinese Han population, which help us to gain insight into the pathogenesis of KC.

Genetic polymorphisms of interleukin-1 beta and osteosarcoma risk.

Osteosarcoma is the most common childhood bone cancer. Interleukin-1 beta (IL-1B) is crucially involved in osteosarcoma carcinogenesis. Whether genetic polymorphisms of IL-1B also influence osteosarcoma risk is unknown. The aim of this study was to investigate the association between IL-1B gene polymorphisms and osteosarcoma risk in Chinese Han patients. A hospital-based case-control study involving 120 osteosarcoma patients and 120 controls was conducted. Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis was performed to detect three IL-1B gene polymorphisms (-31 T/C, -511 C/T and +3954 C/T) in these patients. Patients with osteosarcoma had a significantly lower frequency of -31 CC genotype [odds ratio (OR) = 0.40, 95% confidence interval (CI) = 0.17-0.92; P = 0.03] and -31 C allele (OR = 0.67, 95% CI = 0.46-0.99; P = 0.04) than controls. Patients with osteosarcoma had a significantly lower frequency of -511 TT genotype (OR = 0.40, 95% CI = 0.17-0.95; P = 0.04) than controls. The +3954 C/T gene polymorphisms were not associated with a risk of osteosarcoma. When stratified by Enneking stage, tumour location, histological type, tumour metastasis of osteosarcoma and family history of cancer, no statistically significant results were found. This is the first study to provide evidence for an association of IL-1B gene polymorphisms with osteosarcoma risk.

Current evidences on IL1B polymorphisms and lung cancer susceptibility: a meta-analysis

Interleukin 1, beta (IL1B) plays a key role in mediating acute and chronic inflammation, which is further correlated with lung carcinogenesis. Several polymorphisms on IL1B gene have been identified, and a series of epidemiological studies have examined the association between IL1B polymorphisms and lung cancer risk. However, these findings are inconclusive. To derive a precise estimation of the relationship, a meta-analysis was performed. We summarized 12 eligible publications on three commonly studied IL1B polymorphisms (i.e., -31 T/C, -511 T/C, and +3954 C/T) by searching electronic databases. Combined odds ratio (OR) with 95% confidence interval (CI) was calculated to assess the strength of association between them. Heterogeneity and publication bias were also assessed. We observed a significant association between IL1B polymorphisms and lung cancer. For -31T/C, the overall OR (95% CI) of TT/TC versus CC was 1.23 (1.06-1.43). For +3954 C/T, the overall OR (95% CI) of CC versus TT and CC versus CT/TT were 0.92 (0.86-0.99) and 0.92 (0.86-0.99), respectively. In conclusion, this meta-analysis suggests that the IL1B -31 T/C and +3954 C/T polymorphisms are associated with lung cancer risk. However, larger number of samples and studies with homogeneous lung cancer patients are needed to confirm these findings.

Polymorphisms of Interleukin-1 Beta and Interleukin-17Alpha Genes Are Associated With Restless Legs Syndrome

Dopamine, iron, and inflammatory pathways are considered important to the development of restless legs syndrome (RLS). Recent genetic studies support involvement of dopamine and iron; however, cytokine gene variation in the inflammatory component remains unexplored. A recent study reported a high prevalence of RLS among HIV-infected adults. We estimate occurrence of RLS in an ethnically diverse sample of HIV-infected adults and examine differences in demographic factors, clinical characteristics, and biomarkers relating to dopamine, iron, and inflammation between adults with and without RLS symptoms. A prospective longitudinal study aimed at identifying biomarkers of RLS symptom experience among HIV-infected adults. 316 HIV-positive adults were evaluated using International RLS Study Group criteria. Genes were chosen for hypothesized relationships to dopamine (NOS1, NOS2), iron (HFE) or inflammation-mediated by cytokine genes (interferon [IFN], interleukin [IL], nuclear factor kappa-B [NFKB], and tumor necrosis factor alpha [TNFA]). Similar to general population estimates, 11% of the sample met all four RLS diagnostic criteria. Controlling for race, gender, and hemoglobin, carrying two copies of the minor allele for IL1B rs1143643, rs1143634, or rs1143633 or carrying the minor allele for IL17A rs8193036 was associated with increased likelihood of meeting RLS diagnostic criteria. This study provides preliminary evidence of a genetic association between IL1B and IL17A genes and RLS.

Interleukin-1 Beta Polymorphisms are Associated with Lymph Node Metastasis in Korean Patients with Papillary Thyroid Carcinoma

In this study, we investigated whether single nucleotide polymorphisms (SNPs) of the interleukin-1 beta (IL-1B) were associated with papillary thyroid carcinoma (PTC). We also assessed the relationships between IL-1B SNPs and the clinicopathologic characteristics of PTC patients. Ninety-three PTC patients and 324 controls were recruited. The patients with PTC were dichotomized and compared with respect to the clinicopathologic characteristics of PTC. Seven SNPs in the IL-1B gene were selected and genotyped using direct sequencing. Four SNPs (rs1143627, rs3136558, rs1143633, and rs1143643) in the IL-1B gene were significantly associated with PTC (p < 0.05). In clinicopathologic features, 3 SNPs (rs1143630, rs1143633, and rs1143643) showed a strong relationship with lymph node metastasis of PTC. The genotype and allele frequencies of rs1143630 and rs1143643 remained significantly associated with lymph node metastasis after Bonferroni correction for multiple testing. In haplotype analysis, two linkage disequilibrium blocks (block 1 consisted of rs1143627, rs3917356, and rs1143630; block 2 consisted of rs1143633 and rs1143643) also revealed significant associations with lymph node metastasis. Our results suggest that IL-1B polymorphisms may be associated with the risk of PTC in the Korean population. Especially, IL-1B polymorphisms might be a predictive factor for lymph node metastasis of PTC patients.

Does Helicobacter pylori infection protect against esophageal diseases in Asia?

The speculations on the protective role of Helicobacter pylori against gastroesophageal reflux disease (GERD) originated from epidemiological observations. These studies have shown that the rising trend of GERD is coincident with declining prevalence of H. pylori and peptic ulcer disease in Asia. Furthermore, most case-control and population-based studies suggest a negative association between H. pylori infection and GERD. It is generally believed that the preponderance of cagA+ and vacA+ virulent strains and proinflammatory interleukin-1 beta polymorphism increase the risk of hypochlohydria and protects against the development of GERD in Asian population. Recovery of gastric acid secretion and emergence of reflux esophagitis has been reported after H. pylori eradication in patients with corpus gastritis and atrophic gastritis. Recent studies have also reported that H. pylori eradication leads to recovery of ghrelin secreting cells in the gastric corpus and a rise in plasma ghrelin levels, which may contribute to obesity through its appetite-stimulating action and predispose to GERD. The prevalence of H. pylori infection is generally lower in younger Asians who enjoy improved socioeconomic status and sanitation compared with their older counterparts. The Asian population is probably facing a rising generation with high gastric acid and ghrelin secretion rates. These physiological changes may contribute to increased dietary calorie intake, obesity and increased prevalence of GERD.

Aspirin‐induced peptic ulcer and genetic polymorphisms

There are a few studies of the association between genetic polymorphisms and the risks of acetylsalicylic acid (aspirin)-induced ulcer or its complications. Two single nucleotide polymorphisms (SNP) of cyclooxygenase-1 (COX-1), A-842G and C50T, exhibited increased sensitivity to aspirin and had lower prostaglandin synthesis capacity, lacking statistical significance in the association with bleeding peptic ulcer. A recent Japanese study indicated that the number of COX-1-1676T alleles was a significant risk factor for peptic ulcer in users of non-steroidal anti-inflammatory drugs (NSAIDs). There are some genetic polymorphisms for aspirin resistance, such as platelet membrane glycoproteins, thromboxane A2 (TXA2) receptor, platelet activating factor acetylhydrolase and coagulation factor XIII; however, data on the frequency of gastrointestinal (GI) events in these variants are lacking. Carrying the CYP2C9 variants is reported a significantly increased risk of non-aspirin NSAID-related GI bleeding. The polymorphisms of interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) have been associated with development of peptic ulcer or gastric cancer. In a recent investigation, carriage of the IL-1beta-511 T allele was significantly associated with peptic ulcer among low-dose aspirin users. Hypoacidity in corpus gastritis related to polymorphisms of pro-inflammatory cytokines seems to reduce NSAIDs or aspirin-related injury. Data on which polymorphisms are significant risk factors for GI events in aspirin users are still lacking and further large-scale clinical studies are required.

The Genotypes of IL-1 beta and MMP-3 are Associated with the Prognosis of HCV-related Hepatocellular Carcinoma

Cytokines and matrix metalloproteinases (MMPs) are involved in tumor growth, invasion, and remote metastasis in various cancers. Recently, functional gene polymorphisms in these cytokines and MMPs have been found, and some reports have revealed an association between these polymorphisms and the prognosis of various cancers. In this study, we examined the relationship between the gene polymorphisms of interleukin 1 beta (IL-1b), IL-1 receptor antagonist (IL-1 RN), transforming growth factor beta 1 (TGF-b1), MMP-1, MMP-3, and MMP-9 and the prognosis of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC). We enrolled 92 HCV-related HCC patients in the study, and gene polymorphisms of IL-1b -31 C/T, IL-1 RN variable number of tandem repeats (VNTR), TGF-b1 +869 C/T, MMP-1 -1,607 1G/2G, MMP-3 -1,171 5A/6A, and MMP-9 -1,562 C/T were analyzed. In HCC clinical features, TGF-b1 C carriers and MMP-3 5A carriers had significantly larger HCC diameters than TGF-b1 T and MMP-3 6A homozygotes. In HCC prognosis, IL-1b T homozygotes and MMP-3 5A carriers had a significantly poorer prognosis than IL-1b C carriers and MMP-3 6A homozygotes. Those with a combination of IL-1b T homozygosity and MMP-3 5A had synergistically poorer HCC prognosis. The IL-1b -31 T allele and MMP-3 5A allele are cooperative risk factors for poor prognosis in HCC patients, suggesting that these gene polymorphisms might be potential markers for predicting the prognosis of HCC patients.

Association between interleukin-1 beta polymorphism (+3953) and obesity

It now appears that obesity is associated with a low-grade inflammation of white adipose tissue resulting from chronic activation of the innate immune system as interleukin-1 beta (IL-1). Previous investigations have described a positive association between IL-1β +3953 (C > T) gene polymorphism (rs 1143634) and obesity, suggesting functional effects on fat mass, fat metabolism and body mass. However, it is necessary to determine if these results occur in other populations and if they are influenced by sex and age. Therefore, we performed a case–control study using 880 Caucasian subjects (59.7 ± 11.9 years old) from the Brazilian Aging Research Program (non-overweight = 283, overweight = 334, obese = 263) previously investigated in genetic studies, in whom we analyzed the IL-1β +3953C/T polymorphism. We observed higher T allele (CT/TT) frequency in non-overweight than overweight and obese groups. The odds ratio showed 1.340 (95% CI: 1.119–1.605) times more chance of the obese group being CC carriers compared to non-overweight group independent of sex and age. This study corroborates the idea that the IL-1 system is linked to the development of obesity.

Genetic polymorphisms of interleukin-1β (−511C/T) and interleukin-1 receptor antagonist (86-bpVNTR) in susceptibility to knee osteoarthritis in a Chinese Han population

Osteoarthritis (OA) is a multifactorial disorder in which genetic factors act as important contributors to its onset and progression. Associations between genetic polymorphisms of the interleukin-1 (IL-1) gene cluster and OA susceptibility have been studied continuously in different ethnic groups, yielding controversial results. This study investigated the association of interleukin-1beta (-511C/T) and interleukin-1 receptor antagonist (86-bp VNTR) polymorphisms with knee OA susceptibility in a Chinese Han population. A case-control association study was conducted. The two polymorphisms were genotyped in 453 patients who had primary symptomatic knee OA with radiographic confirmation and in 487 matched controls. Allelic and genotypic frequencies and haplotype distribution were compared between OA and control subjects. For either of the two loci, no significant difference was detected in genotype or allele distribution between knee OA and control groups (all P > 0.05). The haplotype distribution of the two loci showed no difference between the two groups, either. Furthermore, no association between the genotype of the -511 and VNTR polymorphisms and the clinical variables, age, sex, body mass index and Kellgren/Lawrence score was observed in OA patients. The genetic polymorphisms of interleukin-1beta and interleukin-1 receptor antagonist are not risk factors for OA etiology in Han Chinese.

Overexpression of Interleukin-1β Induces Gastric Inflammation and Cancer and Mobilizes Myeloid-Derived Suppressor Cells in Mice

Polymorphisms of interleukin-1beta (IL-1beta) are associated with an increased risk of solid malignancies. Here, we show that stomach-specific expression of human IL-1beta in transgenic mice leads to spontaneous gastric inflammation and cancer that correlate with early recruitment of myeloid-derived suppressor cells (MDSCs) to the stomach. IL-1beta activates MDSCs in vitro and in vivo through an IL-1RI/NF-kappaB pathway. IL-1beta transgenic mice deficient in T and B lymphocytes develop gastric dysplasia accompanied by a marked increase in MDSCs in the stomach. Antagonism of IL-1 receptor signaling inhibits the development of gastric preneoplasia and suppresses MDSC mobilization. These results demonstrate that pathologic elevation of a single proinflammatory cytokine may be sufficient to induce neoplasia and provide a direct link between IL-1beta, MDSCs, and carcinogenesis.

Lack of association polymorphisms of the IL1RN, IL1A, and IL1B genes with knee osteoarthritis in Turkish patients

To examine whether polymorphisms of the interleukin 1 receptor antagonist (IL1RN), interleukin 1 alpha (IL1A) and interleukin 1 beta (IL1B) genes are markers of genetic susceptibility to knee osteoarthritis in Turkish patients. One hundred and seven patients with knee osteoarthritis and 67 controls were studied. Three polymorphisms of IL1A, IL1B, and IL1RN genes were typed from genomic DNA. Allelic frequencies were compared between patients and control subjects. No significant differences were observed in genotype and allele frequencies of the IL1RN VNTR, IL1A+4845, IL1B+3953 genes polymorphisms between patients and controls. Furthermore, we did not detect any association genotypes of the polymorphisms with the clinical, radiological, and laboratory profiles of patients. The present study suggest that the IL1RN VNTR, IL1A+4845, IL1B+3953 genes polymorphisms are not genetic markers of susceptibility to knee osteoarthritis in Turkish patients, and are unrelated to the clinical, radiological, and laboratory characteristics of knee osteoarthritis.