interleukin-1B Gene Polymorphisms Research Articles

Interleukin-1A and interleukin-1B gene polymorphisms in gastroesophageal reflux disease.

Inflammation may play contradictory roles in the pathogenesis of gastroesophageal reflux disease (GERD): gastritis decreases gastric output and reduces the risk of esophagitis, while interleukins may favor mucosal inflammation. The inflammation may cause esogastric motility changes and thus increase the risk of esophagitis. Considering the genetic influence of inflammatory response, we looked for the genetic polymorphisms of IL-1 in GERD manifested as reflux esophagitis. This is a prospective study carried out in GERD and healthy controls. We assessed in these groups the following single nucleotide polymorphisms (SNPs): IL-1A (rs1800587), IL-1B (rs16944), IL-1B (rs1143634) and the VNTR for IL-1RN. Both groups were similar according to biographical data. Reflux esophagitis was confirmed by endoscopy and where necessary by pH-impedance monitoring. Reflux esophagitis was associated only with the polymorphism rs16944. No other correlations with the other three genetic polymorphisms were detected. These data suggest that the diverging effects of proinflammatory factors on the upper digestive tract may have deleterious effect on GERD. The IL-1B (rs16944) SNP correlates with reflux esophagitis.

Association of Interleukin-1B gene Polymorphism with H. pylori infected Dyspeptic Gastric Diseases and Healthy Population.

Objective:The aim of study was to investigate the association of IL 1B gene polymorphism with involvement of H. pylori and other gastric diseases.Methods:Blood samples of dyspeptic patients were collected from endoscopy department of Allied Hospital Faisalabad from January 2017 to January 2019 and were qualitatively assayed for serological detection of CagA H. pylori antibodies. PCR followed by direct sequencing was performed for proinflammatory IL-1B gene polymorphism detection. Sequence analysis was performed in software SnapGene viewer for haplotypes.Results:Demographic characteristics of seropositive patients showed maximum 25% gastritis in age groups of 20-40 years and 41-60 years, predominantly (41.7%) in females. While in seronegative patient’s gastritis (33.3%) was found in age group of 20-40 years mainly in males (41.7%). Among studied groups, higher expression of IL-1B-511 genotype (33.3%) polymorphism was found in healthy individuals as compared to H. pylori seropositive (25%) and seronegative (8.3%). While IL-1B-31 genotype showed maximum 33.3% polymorphism rate in seropositive gastric diseased group. Moreover, haplotypes frequencies IL-1B-511CC and IL-1B-31TT were predominantly (20%) found in seropositive gastric diseased group.Conclusions:In H. pylori seropositive patients, gastric disease was commonly found, however, gastric disease was not only associated with H. pylori as seronegative patients were also carrying gastric complications. Interleukin IL-1B polymorphism was partially associated with H. pylori infection in studied dyspeptic population.

Association of interleukin-1B gene polymorphisms at site 511 with gastroesophageal reflux disease: a meta-analysis

Objectives Multiple factors including genetic and environmental factors play a role in the pathogenesis of gastroesophageal reflux disease (GERD). The objective of this study was to quantitatively evaluate the association between Interleukin-1B-511 gene polymorphism and GERD susceptibility.

Interleukin-1b gene polymorphism and its association with chronic periodontitis in South Indian population

Interleukin-1 beta (IL-1b) is a potent inflammatory mediator and an important polymorphism in the locus +3954 (C/T) of the human IL1B gene has been shown to affect the levels of this cytokine. This functional polymorphism has been associated with the establishment of inflammatory diseases, including periodontal disease, in European, Asian and North American populations. The aim of this study was to investigate the association between the IL1B (+3954) gene polymorphism and the occurrence of different clinical forms of periodontitis in South Indian population. This study employed a cross-sectional design involving individuals from the State of Tamil Nadu in the Southern region of India. Genomic DNA was obtained from 5 ml of venous blood and amplified using the polymerase chain reaction (PCR) with specific primers flanking the locus +3954 of IL1B. PCR products were submitted to restriction endonuclease digestion and analyzed by polyacrylamide gel electrophoresis, to distinguish alleles T and C of the IL1B gene, allowing for the determination of the genotypes and detection of the polymorphism. The chronic periodontitis group displayed a higher percentage of the T allele (28%) than C allele (8.7%). Our data suggested that the polymorphism in the locus +3954 of IL1B gene could be a risk factor for chronic periodontitis in South Indian population. Key words: Gene polymorphism, interleukin 1 beta, periodontitis, allele.

Infection with Specific Helicobacter pylori-cag Pathogenicity Island Strains Is Associated with Interleukin-1B Gene Polymorphisms in Venezuelan Chronic Gastritis Patients

The cag pathogenicity island (cag-PAI) is one of the major virulence factors of Helicobacter pylori, showing considerable geographic variation. We investigated the prevalence of cagA, cagE, and cagT genes of cag-PAI and their association with proinflammatory IL-1B-511/-31/+3954 polymorphisms in Venezuelan chronic gastritis patients from a high-risk gastric cancer region. Presence of cag-PAI genes and IL-1B polymorphisms in 121 biopsy specimens was evaluated by polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (RFLP), respectively. cagA (+) and triple-positive (cagAET (+)) strains were detected in 79.3% and 70.2% of patients, respectively. We found that infection with cagA (+) and cagAET (+) strains was associated (P < 0.05) with hosts harboring both IL-1B +3954C allele and IL-1B-511T/-31C/+3954C haplotype (TCC (+)). The frequency of gastric atrophy was significantly higher (P < 0.020) among cagAET (+)/IL-1B-TCC (+) combined genotype carriers. Carriage of IL-1B +3954C allele and IL-1B-TCC (+) haplotype could favor colonization of bacterial cagAET (+) strains, and the combination of these bacterial and host haplotypes could play a synergistic role in development of premalignant gastric lesions. This work contributes to understanding of the complex interaction between H. pylori virulence factors and cytokine genotypes involved in gastrointestinal diseases.

External apical root resorption and the interleukin-1B gene polymorphism in the Japanese population

External apical root resorption (EARR) is a common consequence of orthodontic treatment. Recently, several studies have reported an association between EARR and an underlying genetic cause. This study investigated whether a single interleukin (IL)-1B gene polymorphism (rs1143634) was associated with EARR in the Japanese population. Genomic DNA, lateral cephalograms, and panoramic radiographs were obtained from 54 Japanese. We measured the EARR in the maxillary central incisors, the mandibular central incisors, and the mesial and distal roots of the mandibular first molar, and analyzed statistically the association between IL-1B polymorphism and EARR. We also examined differences in allelic frequency of this IL-1B polymorphism in a multi-ethnic study population consisting of Japanese, Han Chinese, African American, European Caucasian, and Hispanic individuals. We found no significant difference in the frequency of the IL-1B polymorphism between EARR cases and controls in the Japanese population. We also report marked diversities in the allelic frequencies of the IL-1B polymorphism within the multi-ethnic study population. The European Caucasian population carried the T allele at a frequency of 29.2%, whereas the Japanese population carried the T allele at a frequency of 5.6%. The low frequency of the T allele in Japanese population made it difficult to compare population allelic frequencies among different populations. Further studies are required to confirm our findings and to investigate the effect of other single nucleotide polymorphisms in IL-1B or other genetic risk factors underlying susceptibility to EARR.

Analysis of whole genomic expression profiles ofHelicobacter pylorirelated chronic atrophic gastritis with IL‐1B‐31CC/‐511TT genotypes

Many studies have linked cytokine interleukin-1B gene polymorphisms to H. pylori-related gastric cancer development. The current study evaluated the characterization of whole genomic expression profiles of the premalignant condition: H. pylori-related chronic atrophic gastritis (CAG) with IL-1B-31CC/-511TT genotypes. IL-1B-31/-511 gene polymorphisms were determined by DNA sequences. RNA was extracted and expression profiles were performed using Agilent human whole genomic oligonucleotide microarrays (G4112F). The expression of three samples with H. pylori infection was compared to that of three samples without H. pylori infection from samples of six CAG patients, all with IL-1B-31CC/-511TT genotypes. Differentially expressed genes related to H. pylori-induced CAG with IL-1B-31CC/-511TT genotypes were screened and analyzed further by Gene Ontology (GO) and pathway. Validation of the microarray data was performed using qRT-PCR. A total of 124 differentially expressed genes and 32 GO term annotations were identified between H. pylori positive and negative groups in the six CAG samples with IL-1B-31CC/-511TT genotypes. The signaling pathways identified were oxidative phosphorylation and epithelial cell signaling in H. pylori infection. Five overlapping genes were contained in identified GO terms and pathways: ATP6V0B, NDUFS5, NDUFV2, ATP6V1F and ATP6V1G1. Comparisons of qRT-PCR data and the previously reported data with the results of gene chips support the validity of our microarray data. The H. pylori-related CAG with IL-1B-31CC/-511TT genotypes has shown to be the more malignant phenotype than H. pylori negative CAG with IL-1B-31CC/-511TT genotypes. Mitochondrial energy metabolism probably plays a crucial role as it is the molecular mechanism of host-bacterial interactions.

Interleukin‐1B (IL1B) and interleukin‐6 (IL6) gene polymorphisms are associated with risk of chronic lymphocytic leukaemia

Common polymorphisms in genes encoding for cytokines implicated in the inflammatory response and Th1/Th2 balance might play a role in the development and prognosis of chronic lymphocytic leukaemia (CLL). To test the hypothesis, we investigated 13 single nucleotide polymorphisms (SNPs) in nine of such genes in a population-based case-control study, conducted in the Italian region of Sardinia in 1999-2003. Forty incident CLL cases and 113 population controls were available for study. The following SNPs were selected: IL1A-889C > T, IL1RN 9589A > T, IL1B-31C > T, IL1B-511C > T, IL2-384T > G, IL6-174G > C, IL6-597G > A, IL10-1082A > G, IL10-3575T > A, TNF-308G > A, LTA- 91A > C, LTA 252A > G and CARD15 nt1007. After adjusting by age and gender, individuals homozygous for the IL1B-511T allele run a lower risk of CLL (OR = 0.1, 95% CI 0.0, 0.8, p = 0.032), while risk showed a 4.5-fold increase associated with the genotype homozygous for the IL6-174C allele (OR = 4.5; 95% CI 1.1, 19.3, p = 0.041). Individuals homozygous for the IL6-174C allele and carrying the homozygous IL1B-511C allele showed an 11-fold increase in CLL risk (OR = 11.4, 95% CI 1.9, 69.4, p = 0.008). None of the other interleukin SNPs evaluated showed any association with CLL risk. Large multicentre pooled studies are warranted, achieving the statistical power required to confirm whether IL6 and IL1B gene polymorphisms might play a role in CLL development and prognosis, as well as the null associations herein reported.

Interleukin-1β and Interleukin-1 Receptor Antagonist Gene Polymorphisms and Gastric Cancer: A Meta-analysis

Polymorphisms of interleukin-1B (IL1B) and its receptor antagonist (IL1RN) genes have been inconsistently associated with gastric cancer risk. We examined these associations by performing meta-analyses. Twenty-five studies testing the association between IL1B and/or IL1RN gene polymorphisms and gastric cancer were examined: 14 studies of IL1B-511, 14 studies of IL1B-31, 8 studies of IL1B+3954, and 23 studies of IL1RN. Overall and ethnicity-specific summary odds ratios and corresponding 95% confidence intervals for gastric cancer associated with these polymorphisms were estimated using fixed- and random-effects models. Heterogeneity and publication bias were evaluated. IL1B-511T and IL1RN*2 were associated with gastric cancer risk in Caucasians, but not in Asians. For IL1B-511T, the association in Caucasians was stronger when intestinal-subtype and noncardia gastric cancer cases were examined. A nonsignificant trend was observed between IL1B-31C and gastric cancer in Caucasians. No significant association of IL1B+3954T and gastric cancer risk was detected. Studies with better methodologic characteristics reported stronger effects. There was no evidence of publication bias. IL1B-511T is associated with gastric cancer susceptibility in Caucasians. The meta-analyses suggest that the conflicting results among studies may be explained by variation in allele frequencies among the ethnic groups and variation in tumor types, as well as by the methodologic quality of the studies.

The association of interleukin-1B gene polymorphism and gastric cancers in high and low prevalence regions in China

The association of interleukin-1B gene polymorphism and gastric cancers in high and low prevalence regions in China

Genomic polymorphism within interleukin-1 family cytokines influences the outcome of septic patients.

To determine the allele frequencies and genotype distribution of interleukin-1alpha, interleukin-1beta, and interleukin-1 receptor antagonist gene polymorphism in septic patients. Prospective, consecutive entry study of septic patients in a general intensive care unit. A 14-bed general intensive care unit of a university hospital. Sixty patients with diagnosis of sepsis, admitted to the intensive care unit between 1997 and 1999. None. The polymorphic regions within intron 6 of interleukin-1alpha gene containing variable numbers of a tandem repeat (VNTR) of 46 base pairs, and intron 2 of interleukin-1 receptor antagonist gene containing VNTR of 86 base pairs, were amplified by means of polymerase chain reaction. Alleles A1-4 and RN1-4 were identified according to the size of amplified DNA product. The region containing the AvaI polymorphic site at position -511 of interleukin-1beta gene was amplified by polymerase chain reaction and subsequently digested with AvaI restriction enzyme. The allele frequencies of interleukin-1 receptor antagonist RN2 and genotype RN2/2 were increased in 60 septic patients compared with normal controls (p <.01 and.05, respectively). Allele frequencies or genotype distribution of interleukin-1alpha VNTR gene polymorphism and interleukin-1beta AvaI polymorphism did not differ between septic patients and normal controls. In addition, genotypes A2/2, B2/2, and RN2/2 were associated with a significantly higher mortality rate (70% to 80%) in septic patients. Patients with any two of the three alleles (i.e., A2, B2, and RN2) suffered from much more severe sepsis (as measured by the Acute Physiology and Chronic Health Evaluation II and Multiple Organ Dysfunction Syndrome score) and a higher mortality rate (55% to 65%), whereas septic patients with genotypes A1/1, B1/1, or RN1/1 showed a much lower mortality rate (0% to 13%). Allele interleukin-1RN2, but not interleukin-1A or interleukin-1B gene polymorphism, was associated with susceptibility to sepsis. Alleles A2, B2, and RN2 might be important high-risk genetic markers for sepsis.