Relationship of IL-1 and TNF-α polymorphisms with Helicobacter pylori in gastric diseases in a Brazilian population

It is well known that the risk of development of gastric cancer (GC) in Helicobacter pylori-infected patients depends on several factors. Thus, the aim of this study was to investigate the effect of proinflammatory cytokine gene polymorphisms for IL-1β, IL-1RN and TNF-α on the development of GC in a Brazilian population. A total of 202 biopsies obtained from Brazilian patients with chronic gastritis and GC were included in the study. Infection with H. pylori cagA+ was determined by the polymerase chain reaction (PCR) as previously described. IL-1β, IL-1RN and TNF-α polymorphism genotyping was performed by restriction fragment length polymorphism PCR. Associations between gene polymorphisms, clinical diseases and virulence markers were evaluated using either the χ² test or the Fisher exact test. Our results demonstrated that the IL-1β -511 C/C and IL-1β -511 C/T alleles were associated with chronic gastritis in H. pylori-positive patients (P = 0.04 and P = 0.05, respectively) and the IL-1β -511 C/C genotype was associated with GC (P = 0.03). The frequency of IL-1RN alleles from patients with chronic gastritis and GC indicated that there was no difference between the genotypes of the groups studied. Similar results were found for TNF-α -308 gene polymorphisms. Our results indicate that the IL-1β -511 C/C and C/T gene polymorphisms are associated with chronic gastritis and GC development in H. pylori-infected individuals.

A Interleucina 1-beta mostra uma ação protetora na fase aguda do modelo de epilepsia induzido pela pilocarpina / The il1β have a protective action in the acute phase of the pilocarpine-induced epilepsy model

INTRODUÇÃO: Existem contradições na literatura quanto aos efeitos dos genes il1β e il1rn nas epilepsias. Nosso objetivo foi avaliar os efeitos do silenciamento desses dois genes na fase aguda do modelo de epilepsia induzido pela pilocarpina. MÉTODOS: Para alterar a expressão dos genes il1β e il1rn utilizamos a técnica de interferência por RNA. RESULTADOS: Obtivemos taxas de silenciamento significativas para os dois genes no sistema nervoso central. Observamos efeitos fenotípicos significativos, incluindo a alteração na taxa de mortalidade dos animais 5 dias após a indução do modelo. CONCLUSÕES: A il1β parece exercer um papel protetor na fase aguda do modelo de epilepsia induzido pela pilocarpina.

INTRODUCTION: There is contradictory information regarding the of effects il1β and il1rn in epilepsy. We aimed to evaluate the effect of silencing both genes in the acute phase of the pilocarpine-induced epilepsy model. METHODS: We used RNA interference in order to achieve gene silencing. RESULTS: We obtained significant gene silencing in the central nervous system. In addition, we observed phenotypic effects including differences in mortality rates of animals 5 days after pilocarpine injections. CONCLUSION: Our results indicate that il1β seems to have a protective effect in the acute phase of the pilocarpine-induced epilepsy model.

Distribución deppolimorfismos genéticos de inteleuquina-1 en individuos de la región centroccidental de Venezuela / Distribution of Interleukin-1 Genetic Polymorphisms in Central-Western Region Individuals of Venezuela

Las citoquinas pertenecientes a familia de la interleuquina-1 (IL-1) están codificadas por tres genes diferentes: IL-1A, IL-1B, e IL-1RN, los cuales codifican para IL-1 α, IL-1β, y el antagonista endógeno del receptor de IL-1 (IL-1ra), respectivamente. Las IL-1α e IL-1β actúan como citoquinas pro-inflamatorias, mientras que la IL-1ra se comporta como anti-inflamatoria. Han sido reportados varios polimorfismos bialélicos en los genes de IL-1B, incluyendo IL-1B-511(C/T) e IL-1B+3954(C/T), mientras que IL-1RN presenta en el intrón 2 un polimorfismo VNTR penta-alélico. Los polimorfismos funcionalmente relevantes de estos genes han sido correlacionados con un amplio conjunto de condiciones autoinmunes e inflamatorias crónicas, así como con cáncer. Con el fin de determinar la distribución de estos polimorfismos en la región centroccidental de Venezuela, se estudiaron 100 individuos no relacionados aparentemente sanos. Se extrajo ADN genómico a partir de sangre periférica, y se procedió a la tipificación de los polimorfismos IL-1B-511 e IL-1B+3954 por PCR-RFLP y VNTR de IL-1RN por PCR. Se determinaron las frecuencias alélicas y genotípicas con el programa Arlequín ver. 2.000. Se observó un predominio del alelo T (52%) y del alelo C (82%) en IL-1B-511 y IL-1B+3954, respectivamente. Mientras que para IL-1RN los genotipos más frecuente fueron el 1/1 (47%) y 1/2 (41%). Se compararon los resultados con las frecuencias poblacionales encontradas en otros países, destacándose diferencias significativas con poblaciones de diferente origen étnico. Los resultados podrían proporcionar una referencia valiosa para estudios futuros de asociación con cáncer y enfermedades inflamatorias en Venezuela.

The cytokines belonging to the family of interleukin-1 (IL-1) are encoded by three different genes: IL-1A, IL-1B, and IL-1RN, which encode for IL-1α, IL-1β and the endogenous receptor antagonist for IL-1 (IL-1Ra), respectively. IL-1α and IL-1β operate as pro-inflammatory cytokines, while the IL-1Ra as anti-inflammatory. It has been reported several biallelic polymorphisms in the genes of IL-1B, including IL-1B-511(C/T) and IL-1B+3954(C/T), while IL-1RN presents in intron 2 a penta-allelic VNTR polymorphism. The functionally relevant polymorphisms of these genes have been correlated with a wide range of chronic inflammatory and autoimmune conditions, as well as cancer. In order to determine the distribution of these polymorphisms in the Central-Western region of Venezuela, 100 unrelated apparently healthy individuals were studied. DNA was extracted from peripheral blood, and proceded to the characterization of polymorphisms IL-1B-511 and IL-1B +3954 by PCR-RFLP and VNTR IL-1RN by PCR. Allelic and genotypic frequencies were determined awith the program Arlequin v. 2.0. There was a predominance of T allele (52%) and the C allele (82%) for IL-1B-511 and IL-1B +3954, respectively. While for IL-1RN the more frequent genotypes were 1/1 (47%) and 1/2 (41%). We compare the results with the population frequencies found in other countries, highlighting differences with significant populations of different ethnic origin. These results could provide a valuable reference for future studies of association with cancer and inflammatory diseases in Venezuela.

Association between functional genetic polymorphisms of IL-1B and IL-1RN and susceptibility to gastric cancers / 上海第二医科大学学报

Objective To study the association between functional genetic polymorphisms of IL-1B(T-31C,C-511T),IL-1RN and the susceptibility to gastric cancers. Methods A case-control study was conducted in 180 gastric cancer cases and 308 age-and sex-matched cancer-free controls.Genotypes were detected by PCR-restriction fragment length polymorphism(PCR-RFLP) assays,and association between genotypes,environmental factors and risk of gastric cancers were determined. Results IL-1B T-31C was in strong linkage disequilibrium with IL-1B C-511T(D'=0.862,R2= 0.721,P=0.000).Multivariate logistic regression analysis revealed that the variant genotypes of IL-1B T-31C and C-511T were not significantly associated with risks for gastric cancers(adjusted OR,0.95 and 95% CI,0.62-1.47 for IL-1B T-31C;and adjusted OR,0.85 and 95% CI,0.55-1.31 for IL-1B C-511T).The variant genotypes(1/2,2/2) in IL-1RN were associated with a non-significantly increased risks for gastric cancers(adjusted OR,1.32 and 95% CI,0.71-2.36) in all subjects and with a significantly increased risks for gastric cancers in subjects with H.pylori infection(adjusted OR,2.03 and 95%CI,1.02-4.80).Conclusion The functional genetic polymorphisms of IL-1RN may contribute to the risks of gastric cancers in high-risk population,particularly in those with H.pylori infection.

Interleukin 1 Receptor Antagonist(IL-1ra) Gene Polymorphism in Children with Henoch-Schonlein Purpura Nephritis

PURPOSE: Interleukin 1 receptor antagonist(IL-1ra) is an endogenous antiinflammatory agent that binds to IL-1 receptor and thus competitively inhibits the binding of IL-1alpha and IL-1beta. Allele 2 in association with various autoimmune diseases has been reported. In order to evaluate the influence of IL-1ra gene VNTR polymorphism on the susceptibility to HSP and its possible association with disease severity, manifested by severe renal involvement and renal sequelae, we studied the incidence of carriage rate and allele frequency of the 2 repeats of IL-1ra allele 2(IL1RN*2) of the IL-1ra gene in children with HSP with and without renal involvement. METHODS: The IL-1ra gene polymorphisms were determined in children with HSP with(n= 40) or without nephritis(n=34) who had been diagnosed at Busan Paik Hospital and the control groups(n=163). Gene polymorphism was identified by PCR amplification of the genomic DNA. RESULTS: The allelic frequency and carriage rate of IL1RN*1 were found most frequently in patients with HSP and in controls. The allelic frequency of IL1RN*2 was higher in patients with HSP compared to that of controls(4.7% vs. 2.5%, P=0.794). The carriage rate of IL1RN*2 was higher in patients with HSP compared to that of controls(8.1% vs. 6.8%, P= 0.916). The allelic frequency of IL1RN*2 was higher in patients with HSP nephritis compared to that of HSP(6.3% vs.2.9%, P=0.356). The carriage rate of IL1RN*2 was higher in patients with HSP nephritis compared to that of HSP(10.0% vs. 5.9%, P=0.523). Among 13 patients with heavy proteinuria(>1.0 g), 11 had IL1RN*1, 1 had IL1RN*2 and the others had IL1RN*4. At the time of last follow up 4 patients had sustained proteinuria and their genotype was IL1RN*1. CONCLUSION: The allelic frequency and carriage rate of IL1RN*1 were found most frequently in patients with HSP and in controls. Our study suggests that the carriage rate and allele frequency of the 2-repeats of IL-1ra allele 2(IL1RN*2) of the IL-1ra gene may not be associated with susceptibility and severity of renal involvement in children with HSP.

Investigation of IL-1B (-511, +3954) and IL-1RN Gene Polymorphisms in Korean Psoriasis Patients

BACKGROUND: Psoriasis is an inflammatory skin disorder that is characterized by a marked proliferation of keratinocytes, vascular dilation and leukocyte infiltration. Cytokines play important roles in the pathogenesis of inflammatory disorders. An overexpression of proinflammatory cytokines was characterized in psoriasis plaque. Among these cytokines, IL-1beta is major pro-inflammatory cytokine synthesized during the infection and inflammatory process. The IL-1 receptor antagonist (IL-1Ra) competes for the same IL-1 receptor for IL-1alpha and -1beta, which prevents activation of the target cells. Three single nucleotide polymorphisms (SNPs) in the IL-1beta gene have been reported at position-31, -511 and +3954. Within the IL-1Ra gene (IL-1RN), there is a variable number of tandem repeats (VNTR) of an 86 bp length in intron 2. These polymorphisms related to cytokine production and associated with various diseases. METHODS: We investigated the polymorphisms of IL-1B (promoter -511 and +3954) and IL-1RN on 114 psoriasis patients and -311 healthy normal controls in Korean. We performed PCR-RFLP on single nucleotide polymorphisms (SNPs) of IL-1B (promoter -511 and +3954) and fragment analysis on IL-1RN 86 bp VNTR polymorphism. RESULTS: The frequency of IL-1B-511*1 allele (patients vs. controls; 50.0% vs. 42.3%, RR=1.4) was significantly increased and IL-1B -511*2 allele (patients vs. controls; 50.0% vs. 57.7%, RR=0.7) decreased in psoriasis patients compared to normal controls. We also analyzed the IL-1B -511 polymorphism according to patients' characters (age of onset, sex and family history). The IL-1B -511 alleles were significantly associated in patients with male and family history than health normal controls. There were no significant associations of IL-1B +3954 and IL-1RN polymorphisms with psoriasis patients. CONCLUSION: These results suggest that the polymorphism of IL-1B -511 could be genetic susceptibility to psoriasis in Koreans.