Interleukin-1β Polymorphisms Research Articles

Interleukin-1β Polymorphisms Are Genetic Markers of Susceptibility to Periprosthetic Joint Infection in Total Hip and Knee Arthroplasty.

Periprosthetic joint infections (PJIs) are serious complications of prosthetic surgery. The criteria for the diagnosis of PJI integrate clinical and laboratory findings in a complex and sometimes inconclusive workflow. Host immune factors hold potential as diagnostic biomarkers in bone and joint infections. We reported that the humoral pattern-recognition molecule long pentraxin 3 (PTX3) predicts PJI in total hip and knee arthroplasty (THA and TKA, respectively). If and how genetic variation in PTX3 and inflammatory genes that affect its expression (IL-1β, IL-6, IL-10, and IL-17A) contributes to the risk of PJI is unknown. We conducted a case-control study on a Caucasian historic cohort of THA and TKA patients who had prosthesis explant due to PJI (cases) or aseptic complications (controls). Saliva was collected from 93 subjects and used to extract DNA and genotype PTX3, IL-1β, IL-6, IL-10, and IL-17A single-nucleotide polymorphisms (SNPs). Moreover, the concentration of IL-1β, IL-10, and IL-6 was measured in synovial fluid and plasma. No association was found between PTX3 polymorphisms and PJI; however, the AGG haplotype, encompassing rs2853550, rs1143634, and rs1143627 in IL-1β, was linked to the infection (p = 0.017). Also, synovial levels of all inflammatory markers were higher in cases than in controls, and a correlation emerged between synovial concentration of PTX3 and that of IL-1β in cases only (Spearman r = 0.67, p = 0.004). We identified a relationship between rs2853550 and the synovial concentration of IL-1β and PTX3. Our findings suggest that IL-1β SNPs could be used for the early identification of THA and TKA patients with a high risk of infection.

Association between the interleukin-1B polymorphism at rs16944 T>C and diabetic retinopathy.

Diabetic retinopathy (DR) is a common microvascular complication of diabetes and the leading cause of blindness at working age. DR is considered to be a chronic low-grade inflammatory subclinical disease, and its pathogenesis is related to genetic and environmental factors. Interleukin (IL)-1 is an important inflammatory cytokine. An association between DR and the rs16944 (IL-1B-511) T>C gene polymorphism has not been reported. The aim of this study was to investigate the association between the rs16944 T>C gene polymorphism and DR in the Han population in southwest China. Participants in this study were 272 patients with DR, 274 patients with type 2 diabetes mellitus (T2DM), and 335 healthy controls (NC). The polymerase chain reaction-restriction fragment length polymorphism method was used to detect the rs16944 T>C genotype of participants. The distribution frequencies of the rs16944 T>C genotype and allele were significantly different among the three groups (p < .05). The distribution frequency of TT, CT, CC genotype (χ2 = 9.893, p = .007; χ2 = 6.567, p = .037) and each allele (χ2 = 5.585, p = .018; χ2 = 9.187, p = .002) in the DR group was significantly different from the NC and T2DM groups, respectively. Logistic regression analysis showed that the TT + CT genotype was a risk factor for DR, with an odds ratio of 1.731 (95% confidence interval 1.140-2.627, p = .01). The rs16944 T>C gene polymorphism may be associated with DR, and the TT+CT genotype may increase the risk of DR.

Association of specific haplotype of tumor necrosis factor-α and interleukin-1β polymorphisms with Helicobacter pylori infection and gastric carcinogenesis.

The Helicobacter pylori infection and cytokine-mediated inflammatory responses play significant roles in the pathogenesis of gastric cancer (GC). This study was performed to determine the association between the risk of GC and genetic polymorphisms in interleukin (IL)-1β and tumor necrosis factor-alpha (TNF-α). The polymorphisms of IL-1β and TNF-α genes were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 290 patients who underwent endoscopy. Infection with H. pylori was diagnosed by histological analysis, rapid urease test, and PCR of gastric biopsy samples. Quantitative real-time PCR was performed to determine the relative mRNA expression levels. No significant difference was detected in allele frequency and genotype of all studied polymorphisms between chronic gastritis (CG), GC and healthy individuals. IL-1β mRNA was down-regulated in both gastritis (relative quantification (RQ)=0.447) and the GC groups (RQ=0.151). In contrast, the expression of TNF-α was up-regulated in the GC group (RQ=2.817) compared to the gastritis group (RQ=0.861). The studied single-nucleotide polymorphisms are not risk factors for development of CG and GC. However, H. pylori infection causes a huge increase in the TNF-α expression in GC patients.

Association between Interleukin-1β Polymorphism at Rs16944 and Glucose Metabolism: A Cohort Study

ABSTRACT Background This study explored the correlation between the interleukin-1β gene rs16944 polymorphism and diabetes through epidemiological and follow-up investigations. Methods The study was conducted on 600 subjects with normal glucose metabolism recruited from participants of the Risk Evaluation of cAncers in Chinese type 2 diabeTic Individuals: A lONgitudinal (REACTION) study in Luzhou, China in 2011. All subjects received a unified standardized questionnaire, physical examination, laboratory examination, and follow-up in 2016. Subjects were divided into normal glucose metabolism (NC), pre-diabetes (PDM), and type 2 diabetes mellitus (T2DM) groups according to their glucose metabolism after follow-up. The IL-1β gene rs16944 polymorphism was analyzed using the polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) technique. Results After follow-up, 386, 156, and 58 cases were observed in the NC, PDM, and T2DM groups, respectively. Serum IL-1β levels were compared to baselines at follow-up in the 3 groups; the difference in the T2DM group was statistically significant. The frequency distributions of the IL-1β gene rs16944 genotypes, i.e., CC, CT, and TT, were significantly different in the 3 groups, and the distributions in the T2DM and NC groups were significantly different. The frequency distributions of the C and T alleles of IL-1β rs16944 were not significantly different. Logistic regression analysis identified the CC+CT genotype as an independent risk factor for the development of diabetes in patients with normal glucose metabolism (OR = 2.457, 95% CI: 1.238–4.877). Conclusions The IL-1β gene rs16944 C/T polymorphism may cause genetic susceptibility to T2DM in the Luzhou population. The CC+CT genotypes may increase T2DM risk.

Polymorphism of Interleukin 1B May Modulate the Risk of Ischemic Stroke in Polish Patients.

Background and Objectives: Inflammation plays a crucial role in the pathophysiology of ischemic stroke (IS). Interleukin-1B and interleukin-1 receptor antagonists are key factors in inflammatory processes. Aims: The aims of our study were to evaluate the relationship between genetic variation in interleukin-1B (IL1B) rs1143627 and interleukin-1 receptor antagonist (IL1RN) variable-number-tandem-repeats (VNTR), and overall IS and subtype prevalence rates. Materials and Methods: The analysis included 147 hospitalized Polish patients with IS diagnosed using conventional criteria. The control group consisted of 119 healthy subjects. Genotypes were determined by polymerase chain reaction. Results: A significant association between rs1143627 and stroke was found. The -31C IL1B polymorphism showed an association with overall IS, OR = 2.30 (1.36–3.87) p = 0.020. An association was also detected for LVI (large vessel infarction) subtypes of stroke. After risk factor adjustment (age, diabetes mellitus, dyslipidemia), the C allele was found to be an independent risk factor for LVI, OR = 1.99 (1.05–3.79) p = 0.036. Significant association was not observed between IL1RN alleles and IS. Conclusions: Our results suggest that the C allele of IL1B rs1143627 may be associated with susceptibility to overall IS and LVI subtypes of stroke in the Polish population.

Interleukin 1β polymorphism and serum level are associated with pediatric asthma.

Interleukin-1 is a pro-inflammatory cytokine found in two forms (α and β). The α form is mainly cell-bound, whereas IL-1β is primarily secreted by macrophages in response to immune system stimulation. We hypothesized that polymorphic variants of interleukin 1 genes may play a role in childhood asthma risk. The aim of this study was to investigate if IL-1α and β polymorphism is associated with asthma in a pediatric population and if the genotype affects its serum level. The studied population included 310 children aged 6-18 years old (152 with asthma and 158 healthy children). Genotypes were determined with real-time PCR method using TaqMan Genotyping Assays. Serum level was measured with ELISA Set. Statistical analysis was done in Statistica v.12.0. Linkage disequilibrium and haplotype analysis was done in Haploview v. 4.2. We found that three IL-1β polymorphisms rs1143634, rs1143633, and rs1143643 were associated with allergic asthma risk (P = 0.034; OR = 1.523; P = 0.024, OR = 1.477; 0.044, OR = 1.420, respectively). We also found a strong linkage disequilibrium between these polymorphisms and CAC haplotype was associated significantly with asthma risk (P = 0.023). For IL1α, we did not observe association with asthma. We then analyzed if IL-1β expression was altered in serum and we found that asthmatic children showed significantly higher IL-1β levels than healthy controls (P = 0.047). No association with asthma was observed for IL-1 α variants. This study indicates that IL-1β gene polymorphism may affect allergic asthma risk in children.

P.1.a.012 - Interleukin-6 and interleukin-1B polymorphisms show different interaction patterns with stressors on trait anxiety

The aim of the present study was to examine the prognostic significance of heart rate and its trend in heart transplantation.This observational study enrolled 170 patients who received a bicaval heart transplant between 1995 and 2005; all were in sinus rhythm. The resting heart rate was determined via electrocardiography at the end of the first posttransplant year and annually until the tenth year. Cox analysis was used to evaluate the incidence of adverse events with a mean (standard deviation) follow-up of 8.9 (3.1) years. The primary study end point was the composite outcome of death or graft dysfunction.The resting heart rate at the end of the first posttransplant year was an independent predictor of the primary composite end point (hazard ratio = 1.054; 95% confidence interval, 1.028-1.080; P < .001) and was significantly associated with total mortality (hazard ratio = 1.058; 95% confidence interval, 1.030-1.087; P < .001) and mortality from cardiac causes (hazard ratio = 1.069; 95% confidence interval, 1.026-1.113; P = .001), but not with graft dysfunction (hazard ratio = 1.028; 95% confidence interval, 0.989-1.069; P = .161). For patients with a heart rate ≥ 105 or < 90 bpm vs those with 90-104 bpm, the hazard ratios of the primary end point were 2.233 (95% confidence interval, 1.250-3.989; P = .007) and 0.380 (95% confidence interval, 0.161-0.895; P = .027), respectively. Heart rate tended to decrease in the first 10 years after transplantation (P = .001). Patients with a net increase in heart rate during follow-up showed a higher incidence of adverse events.An elevated heart rate is an adverse prognostic marker after heart transplantation.Estudiar la evolución y el significado pronóstico de la frecuencia cardiaca tras el trasplante cardiaco.Estudio observacional de 170 pacientes que recibieron un trasplante cardiaco bicavo entre 1995 y 2005; todos estaban en ritmo sinusal. La frecuencia cardiaca en reposo se determinó a partir de electrocardiogramas al final del primer año tras el trasplante y anualmente hasta el décimo año. Mediante análisis de Cox, se evaluó la incidencia de eventos adversos en un seguimiento medio de 8,9 ± 3,1 años. El evento principal del estudio fue la variable combinada muerte o disfunción del injerto.La frecuencia cardiaca en reposo, medida al final del primer año tras el trasplante, fue un predictor independiente del evento combinado principal (hazard ratio = 1,054; intervalo de confianza del 95%, 1,028-1,080; p < 0,001). Se observó una asociación estadísticamente significativa con la mortalidad total (hazard ratio = 1,058; intervalo de confianza del 95%, 1,030-1,087; p < 0,001) y con la mortalidad por causas cardiacas (hazard ratio = 1,069; intervalo de confianza del 95%, 1,026-1,113; p = 0,001), pero no con la disfunción del injerto (hazard ratio = 1,028; intervalo de confianza del 95%, 0,989-1,069; p = 0,161). Para los pacientes con frecuencia cardiaca ≥ 105 y < 90 lpm frente a aquellos con 90-104 lpm, las hazard ratio del evento principal fueron, respectivamente, 2,233 (intervalo de confianza del 95%, 1,250-3,989, p = 0,007) y 0,380 (intervalo de confianza del 95%, 0,161-0,895; p = 0,027). Este parámetro presentó una tendencia decreciente en los primeros 10 años del trasplante (p = 0,001). Los pacientes con incremento neto de frecuencia cardiaca en el seguimiento mostraron mayor incidencia de eventos adversos.La frecuencia cardiaca elevada es un marcador pronóstico adverso tras el trasplante cardiaco.

Association between interleukin-1β polymorphisms and gastric disease in children: A correlation with Helicobacter pylori

ObjectiveTo investigate an association between the interleukin-1β (IL-1β)−511 T>C (rs16944), −31 C>T (rs1143627), and/or interleukin-1 receptor antagonist (IL-1RA) polymorphisms and gastritis and then to correlate any associations with the presence of Helicobacter pylori (H. pylori), cagA and vacA genes. MethodsGastric biopsies were obtained from 377 children with gastric symptoms including 152 males and 225 females aging from 1–15 years with the mean age of (9.41 ± 4.29) years. To characterize the −511 T>C, −31 C>T, and IL-1RA polymorphisms, the PCR-RFLP and PCR-VNTR methods were used. PCR was also used for the diagnosis of H. pylori and to determine whether cagA and vacA genes were present. ResultsThe histopathological analysis revealed 206 patients (54.6%) with gastritis and 171 patients (45.4%) with normal gastric tissue. Subjects carrying the −511 T/T genotype were associated with a risk of gastritis (odds ratio (OR) = 2.75, 95% confidence interval (CI) 1.45–5.18, P = 0.0035). Similar results were found in subjects carrying −31 C/C (OR = 2.27, 95% CI 1.13–4.54, P = 0.0440). However, the IL-1RA polymorphism did not seem to be associated with gastric disease (OR = 1.38, 95% CI 0.58–3.26, P = 0.2400). ConclusionsThis data suggests that IL-1β gene cluster polymorphisms and, more specifically, interactions between these polymorphisms and H. pylori may be predictors of gastritis risks, which possibly play a relevant role in the susceptibility to or the development of gastric disease early in life.

A study of the effect of the genes of inflammatory proteins on basic personality dimensions

The present research examines the association between two basic dimensions of personality and genes of inflammatory cytokines and mediators reported to be elevated in schizophrenia and affective disorders. Genes of interleukin-1B (IL-1B), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), C-reactive protein (CRP) and alpha 1-antitrypsin (A1AT) were studied. A total of 639 healthy subjects, aged from 17 to 69 years, participated in the study. The following polymorphisms were genotyped: IL-1B С-511Т (rs16944) and С3954Т (rs1143634), IL-6 G-174C (rs1800795), TNF-α G-308A (rs1800629), CRP (rs279452), A1AT 374G/A (rs709932). Basic personality dimensions Extraversion and Neuroticism were assessed using the Eysenck Personality Inventory. The levels of Extraversion and Neuroticism were not associated with IL-1B, IL-6, TNF-α G and CRP polymorphisms. The association between the A1AT 374G/A polymorphism and Extraversion (р=0.036) was shown. There was a trend towards the association between the A1AT 374G/A polymorphism and Neuroticism (p=0,05) in women. Because this is the first study of the effect of IL-1B, IL-6, TNF-α and A1AT on personality dimensions, the results should be considered as preliminary and need to be replicated.

Interleukin 1β (+3954, −511 and −31) polymorphism in chronic periodontitis patients from North India

Objective. Several studies have implicated the role of interleukin-1 in various chronic diseases including periodontitis. The present study was carried out with an aim to evaluate the role of interleukin 1β polymorphisms, namely +3954C/T, −511C/T and −31T/C, in the development of chronic periodontitis. Materials and methods. Twenty-nine chronic periodontitis patients and 31 healthy controls of North Indian origin from Chhattisgarh were recruited for the study. The genotypes for the three variants were determined using the PCR-RFLP technique and the strength of association between genotypes and periodontitis was determined by odds ratio with 95% confidence interval (CI) and chi-square analysis. Results. Analysis for the +3954 allelic and genotypic frequencies of the polymorphism revealed a significant difference in the CT genotype between periodontitits patients and controls (p = 0.03). A significant difference was also observed in the allelic frequencies between the two groups (p = 0.02). For the −511 site, TT genotype revealed a significant association with the disease (p = 0.01). A significant association was also found following the co-dominant model (p = 0.007). However, the −31 polymorphism revealed no significant difference between patients and controls. Conclusions. In conclusion, the present study suggests a strong association of the TT genotype of −511 and CT genotype of +3954 variant of interleukin 1β with chronic periodontitis. However, the −31 variant did not show a significant association with the disease.

The Impact of Interleukin 12B (1188A>C), Interleukin 16 (-295T>C), and Interleukin 18 (607C>A, 137G>C) Gene Polymorphisms on Long-Term Renal Transplant Function and Recipient Outcomes

BackgroundInflammatory mediators play an important role in kidney graft outcome. The cytokine and chemokine gene polymorphisms are associated with variable production, activity, expression, or ligand-receptor affinity. Genetic variation in the DNA sequence of the interleukin 12B (IL12B), interleukin 16 (IL16), and interleukin 18 (IL18) genes may lead to altered cytokine production and activity. These variations can lead to changes in individual patient outcomes after kidney transplantation. It is known that polymorphisms of interleukins have an influence on inflammatory diseases, eg, Crohn's disease, diabetes, and asthma. AimThe aim of this study was to evaluate the correlation between IL12B, IL16, and IL18 gene polymorphisms with delayed graft function (DGF), acute rejection episodes (AR), and chronic rejection episodes (CR). Materials and MethodsA total of 267 (38.6% women, 61.4% men) recipients were included in the study. Cadaveric kidney transplantations were performed at the Department of General Surgery and Transplantation. Polymerase chain reaction was used to determine gene polymorphisms of IL12B (rs3212227), IL16 (4778889), and IL18 (rs1946518, rs187238) in 2 mL of serum. Statistical significance (P < .05) was analyzed by logit regression, ANOVA and odds ratio (OR) of χ2 with Yates correction (95% confidence interval). ResultsRegression analysis revealed no significance between AR/DGF/CR and IL-2B, IL16, IL18rs1946518, and IL18-rs187238 (P > .05). The CR group, AA vs CC genotype of IL18 (rs1946518), had an OR = 2.35 (P = .04). AR and DGF groups had no significance in OR. ConclusionsThere was no statistical significance between IL12B, IL16, and IL18 (rs187238) gene polymorphisms and kidney graft outcome after transplantation. Presence of AA genotype (IL18–rs1946518) is connected with a 2.35 times higher risk of CR occurrence.

Associations between interleukin-23R and interleukin-12B polymorphisms and psoriasis susceptibility: a meta-analysis

Objective: The aim of this study was to determine whether interleukin (IL)-23 R and IL-12B polymorphisms confer susceptibility to psoriasis.Methods: The authors conducted a meta-analysis on associations between the IL-23 R and IL-12B polymorphisms and psoriasis susceptibility.Results: A total of 14 comparison studies were included in this meta-analysis. The meta-analysis identified a significant association between psoriasis and 2 alleles of the rs11209026 and rs7530511 polymorphisms in Europeans (odds ratio [OR] = 0.624, 95% confidence interval [CI] = 0.565–0.697, p < 1.0 × 10−8; OR = 0.804, 95% CI = 0.743–0.869, p = 3.0 × 10−7, respectively). Meta-analysis of IL-12B showed a significant association between the 2 alleles of the rs6887695 and rs3212227 polymorphisms and the risk of developing psoriasis (OR = 0.710, 95% CI = 0.673–0.749, p < 1.0 × 10−8; OR = 0.684, 95% CI = 0.639–0.731, p < 1.0 × 10−8, respectively). Stratification by ethnicity identified an association between the rs6887695 and rs3212227 polymorphisms and psoriasis in Europeans.Conclusions: This meta-analysis showed that the IL-23 R (rs11209026 and rs7530511) polymorphisms are associated with psoriasis risk in Europeans and that the IL-12B (rs6887695 and rs3212227) polymorphisms are associated with susceptibility to psoriasis in Europeans.

Association between interleukin-1B polymorphisms and chronic obstructive pulmonary disease: a meta-analysis

To explore the association between the -511C/T, -31T/C and +3954C/T polymorphisms of interleukin-1B (IL-1B) gene and chronic obstructive pulmonary disease (COPD) using the method of meta-analysis. Comprehensive searches were performed of PubMed, Embase, Ovid, Wanfang and Chinese journal full-text database to retrieve the related case-control studies. The pooled odds ratios were performed respectively for allele comparison, additive genetic model, dominant genetic model and recessive genetic model and subgroup analysis was also performed by ethnicity. Seven case-control studies were included for meta-analysis. Pooled analysis showed that neither -511C/T, -31T/C nor +3954 C/T polymorphisms increased the susceptibility to COPD. In the subgroup analysis by ethnicity, significant risks were found in the Caucasian population for -511C/T T allele (OR = 1.76, 95%CI 1.22 - 2.54, P = 0.002), but not in the Asian population (OR = 0.94, 95%CI 0.64 - 1.38, P = 0.736). Significant risks were also found in the Caucasian population for -31T/C C allele (OR = 0.62, 95%CI 0.40 - 0.97, P = 0.035), but not in the Asian population (OR = 1.06, 95%CI 0.89 - 1.26, P = 0.533). IL-1B polymorphisms may play a role in the susceptibility of COPD in an ethnicity-specific manner. In the Caucasian population, the risk of COPD was associated positively with the IL-1B -511C/T T allele and negatively with the IL-1B -31T/C C allele.

Gene-Gene Interaction and Functional Impact of Polymorphisms on Innate Immune Genes in Controlling Plasmodium falciparum Blood Infection Level

Genetic variations in toll-like receptors and cytokine genes of the innate immune pathways have been implicated in controlling parasite growth and the pathogenesis of Plasmodium falciparum mediated malaria. We previously published genetic association of TLR4 non-synonymous and TNF-α promoter polymorphisms with P.falciparum blood infection level and here we extend the study considerably by (i) investigating genetic dependence of parasite-load on interleukin-12B polymorphisms, (ii) reconstructing gene-gene interactions among candidate TLRs and cytokine loci, (iii) exploring genetic and functional impact of epistatic models and (iv) providing mechanistic insights into functionality of disease-associated regulatory polymorphisms. Our data revealed that carriage of AA (P = 0.0001) and AC (P = 0.01) genotypes of IL12B 3′UTR polymorphism was associated with a significant increase of mean log-parasitemia relative to rare homozygous genotype CC. Presence of IL12B+1188 polymorphism in five of six multifactor models reinforced its strong genetic impact on malaria phenotype. Elevation of genetic risk in two-component models compared to the corresponding single locus and reduction of IL12B (2.2 fold) and lymphotoxin-α (1.7 fold) expressions in patients'peripheral-blood-mononuclear-cells under TLR4Thr399Ile risk genotype background substantiated the role of Multifactor Dimensionality Reduction derived models. Marked reduction of promoter activity of TNF-α risk haplotype (C-C-G-G) compared to wild-type haplotype (T-C-G-G) with (84%) and without (78%) LPS stimulation and the loss of binding of transcription factors detected in-silico supported a causal role of TNF-1031. Significantly lower expression of IL12B+1188 AA (5 fold) and AC (9 fold) genotypes compared to CC and under-representation (P = 0.0048) of allele A in transcripts of patients' PBMCs suggested an Allele-Expression-Imbalance. Allele (A+1188C) dependent differential stability (2 fold) of IL12B-transcripts upon actinomycin-D treatment and observed structural modulation (P = 0.013) of RNA-ensemble were the plausible explanations for AEI. In conclusion, our data provides functional support to the hypothesis that de-regulated receptor-cytokine axis of innate immune pathway influences blood infection level in P. falciparum malaria.

Interactions of interleukin-12A and interleukin-12B polymorphisms on the risk of intracranial aneurysm

Several lines of evidence indicate that inflammatory processes play pivotal role in the development of intracranial aneurysm (IA). Recently, polymorphisms in the interleukin-12 (IL-12) gene were shown to be associated with immune-mediated inflammatory disease. The aim of this study was to investigate the interactions of IL-12A and IL-12B polymorphisms on the risk of IA in a Chinese population. A total of 422 individuals (including 164 patients with IA and 258 controls) were involved in the study. The polymorphisms (i.e., rs2243115 and rs568408 in IL-12A and rs3212227 in IL-12B) were genotyped by polymerase chain reaction-restriction fragment length polymorphism assay and DNA sequencing. We found an association of the AC/CC genotypes and C allele of IL-12B rs3212227 with an increased risk of IA, compared with the AA genotype and A allele (AC/CC vs. AA: OR = 2.09, 95 % CI: 1.29-3.38; C vs. A: OR = 1.45, 95 % CI: 1.10-1.91). Moreover, a significant gene interaction of IL-12A and IL-12B was evident on the risk of IA, and subjects carrying variant genotypes of IL-12B rs3212227 had an increased risk of IA. In the stratified analysis by gender, the IL-12B rs3212227 AC/CC genotypes had an increased risk of IA compared with the AA genotype in male patients (AC/CC vs. AA: OR = 4.63, 95 % CI: 1.92-11.16). These findings suggest that the IL-12A and IL-12B independently and jointly be involved in the susceptibility to IA.

Association of interleukin 1β polymorphisms and haplotypes with Alzheimer's disease

Our study aimed to associate IL-1β and IL-1RN polymorphisms with AD disease in comparison with elderly control group from São Paulo — Brazil. We genotyped 199 Alzheimer's disease (AD) patients, 165 elderly control and 122 young control samples, concerning VNTR (IL-1RN) and −511C>T and −31T>C (IL-1β) polymorphisms. Our findings revealed that −511C/−31T/2-repetitions VNTR haplotype had a protective effect for AD when compared to EC (p=0.005), whereas −511C/−31C/1-repetition VNTR haplotype was associated as a risk factor for AD (p=0.021). Taken together, we may suggest that there is a relevant role of IL-1 genes cluster in AD pathogenesis in this Brazilian population.

MCP1 SNPs and pulmonary tuberculosis in cohorts from West Africa, the USA and Argentina: lack of association or epistasis with IL12B polymorphisms.

The monocyte chemotactic protein-1 (MCP-1) is a chemokine that plays an important role in the recruitment of monocytes to M. tuberculosis infection sites, and previous studies have reported that genetic variants in MCP1 are associated with differential susceptibility to pulmonary tuberculosis (PTB). We examined eight MCP1 single nucleotide polymorphisms (SNPs) in a multi-ethnic, case-control design that included: 321 cases and 346 controls from Guinea-Bissau, 258 cases and 271 controls from The Gambia, 295 cases and 179 controls from the U.S. (African-Americans), and an additional set of 237 cases and 144 controls of European ancestry from the U.S. and Argentina. Two locus interactions were also examined for polymorphisms in MCP1 and interleukin 12B (IL12B), another gene implicated in PTB risk. Examination of previously associated MCP1 SNPs rs1024611 (−2581A/G), rs2857656 (−362G/C) and rs4586 (+900C/T) did not show evidence for association. One interaction between rs2857656 and IL12B SNP rs2288831 was observed among Africans but the effect was in the opposite direction in Guineans (OR = 1.90, p = 0.001) and Gambians (OR = 0.64, p = 0.024). Our data indicate that the effect of genetic variation within MCP1 is not clear cut and additional studies will be needed to elucidate its role in TB susceptibility.

Postorthodontic External Root Resorption in Root-filled Teeth Is Influenced by Interleukin-1β Polymorphism

IntroductionExternal apical root resorption (EARR) is a frequent iatrogenic effect of orthodontic treatment. The way root-filled teeth respond to orthodontic forces with respect to EARR has been reported as varying widely between individuals. Genetic variants in the interleukin-1 gene have been associated with an increased risk of experiencing postorthodontic EARR on vital teeth. The objective of this study is to determine whether variants in the interleukin-1 gene have a positive or negative influence on EARR on teeth that have been endodontically treated. MethodsNinety-three orthodontic patients underwent genetic screening for 2 single nucleotide polymorphisms (rs1800587, rs1143634) in the IL1 gene cluster. Subjects were divided into 2 groups depending on the presence (affected group) or absence (control group) of more than 2 mm of EARR on root-filled teeth after orthodontic treatment as shown by radiography. Logistic regression analysis was used to obtain adjusted estimates of EARR and IL1 polymorphisms. Allele frequencies, genotype distributions, and adjusted odds ratios were also calculated (95% confidence interval). ResultsNo positive or negative statistical association was found between postorthodontic treatment EARR in root-filled teeth and genetic variations in IL1A (P > .05). A direct relationship was found for the IL1B gene in the comparative analysis of homozygous subjects (2/2[TT]) and (1/1[CC]), which led to an increased risk of experiencing postorthodontic treatment EARR in root-filled teeth (odds ratio = 11.59; P = .006; confidence interval, 95%) and (odds ratio = 2.54; P = .035; confidence interval, 95%), respectively. ConclusionsThe development of EARR in subjects with root-filled teeth who undergo orthodontic treatment might be attributable to genetic variations in the interleukin-1β gene (rs1143634).

Prognostic role of interleukin-1B and interleukin-1-receptor antagonist polymorphisms in localized gastric cancer.

10623 Background: Interleukin-1b (IL1b) and interleukin-1 receptor antagonist (IL1-RN) polymorphisms have been suspected to play a role in prognostication of advanced gastric cancer (GC). Here, we sought to determine the prognostic role of these polymorphisms in localized GC. Methods: 62 patients (pts) were enrolled in this prospectively planned analyses. Pts were treated with peri-operative neoadjuvant and adjuvant chemotherapy between 2006 and 2010. All pts signed written informed consent for genetic analyses. DNA for genotyping was extracted from whole blood samples. Genotyping was performed using PCR-based methods. The primary objective was to analyze the association between genotypes and clinical outcome measured by overall survival (OS). Results: Median age was 59 years. Majority of pts were male (81%). 86% of pts were treated with epirubicine in combination with cisplatin or oxaliplatin and 5-fluorouracil or capecitabine. 14% were treated without epirubicine. Pts were assigned to receive peri-operative treatment consisting of 3 neoadjuvant and 3 adjuvant chemotherapy cycles. Median OS of the whole study population was 32.0 months [95%CI (28.0;35.9)]. IL1bC-511T, IL1bT-31C and IL1-RN polymorphisms were in strong linkage disequilibrium. In fact, the wildtype genotype IL-1b-511CC genotype was observed exclusively in combination with the wt IL1b-31TT and vice versa and a strong correlation with the IL1-RN L/L genotype was observed. Wildtype genotypes were associated with favourable median OS. Multivariate cox regression analyses revealed following factors as independent prognosticators of OS: presence of N2 status with a HR of 5.6 [95%CI (1.5;21.1); p=0.01], age with a HR of 1.6 [95%CI (1.2;2.1); p<0.001] and presence of the IL1-RN L/L genotype with a HR of 0.2 [95%CI (0.1; 0.5), p=0.001]. Median OS in pts with the homozygous wt genotype IL1-RN L/L was not reached whereas median OS in 2/L or 2/2 pts was 32 months [95%CI (18.1;45.9); p=0.09; log-rank test]. Conclusions: Our results confirm the prognostic role of IL1b and IL1RN polymorphisms in localized GC. These polymorphisms might play a crucial role in the guidance of multimodal treatment of localized GC.

More than Inflammation: Interleukin-1β Polymorphisms and the Lipid Metabolism

More than Inflammation: Interleukin-1β Polymorphisms and the Lipid Metabolism