Tu1427 Interleukin-10 and TGF-1 Anti-Inflammatory Cytokine Gene Polymorphisms are Involved in the Pathophysiology of Irritable Bowel Syndrome: A Meta-Analysis (original) (raw)
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Neurogastroenterology & Motility, 2012
Background Low-grade inflammation has been increasingly implicated in the pathophysiology of irritable bowel syndrome (IBS). Imbalances of proand anti-inflammatory cytokines and polymorphisms in cytokine genes have been reported in IBS; however, these findings have not been consistently observed. This may be due to small sample sizes and differences in ethnicities. Therefore, we performed a meta-analysis on the studies that investigated cytokine gene polymorphisms in IBS patients compared to healthy controls. Methods A PubMed and EMBASE search was performed, and cytokine gene polymorphisms, which had been investigated in at least two case-control studies, were evaluated. Pooled odds ratios (OR) for the genotypes were calculated using random-or fixedeffects models. Key Results Five studies that investigated interleukin-10 (IL-10;)1082 G/A), transforming growth factor-b1 (TGF-b1; +869 T/C and +915 G/C) and tumor necrosis factor (TNF;)308 G/A) polymorphisms in IBS patients and controls were included. High producer IL-10 ()1082 G/G; OR: 0.64 [95% CI: 0.48-0.87]) was significantly associated with a decreased risk of IBS. The intermediate producer TGF-b1 (+915 G/C) genotype showed a tendency toward decreasing the risk of IBS. No associations were found between TNF ()308 G/A) genotypes and IBS in the whole meta-analysis although an analysis of Asian studies revealed an association between TNF ()308 G/ A and G/G) genotypes and IBS (OR: 0.50 [95% CI: 0.29-0.85]), and 1.82 [95% CI: 1.08-3.07], respectively). Conclusions & Inferences This meta-analysis indicates a role for IL-10 polymorphisms in IBS in general and TNF in Asian populations. Whether or not gene polymorphisms are associated with alterations in cytokine levels leading to functional effects at the level of the gut needs further investigation.
https://www.ijhsr.org/IJHSR\_Vol.7\_Issue.3\_March2017/IJHSR\_Abstract.016.html, 2017
Aims: The current study conducted to determine the frequency of the IL-10 (-1082G/A) and TNF-α (-308G/A) polymorphisms in subjects with IBS in Sudan. Methods: After giving written consent, a total of 71 patients with symptoms of IBS according to the Rome III criteria and 40 controls were enrolled. DNA was extracted from peripheral blood leucocytes of subjects using salting out method. Polymorphisms were determined by PCR-RFLP method. SPSS software program was used for statistical analysis. Results: Patients with irritable bowel syndrome had significantly reduced frequencies of the high producer genotype for interleukin 10 than controls (21% v 32%; p=0.003). there was no significant difference in the frequency of the genotypes or the alleles of the IL-10 (-1082G/A) and the TNF-α (-308G/A) polymorphisms between IBS and the controls, however it was demonstrated that the high producer (AA) TNF α genotype was more prevalent in IBS patients compared to healthy controls (8.5% VS zero). IBS patients were classified as IBS-D (53.5 %), IBS-C (18.3 %) and IBS-A/M (28.2 %) and there were no statistical differences IBS subgroups, were found among these IBS subgroups 57% of patients had family history of IBS. Conclusions: The frequency of the IL-10 (-1082G/A) and TNF-α (-308G/A) genotypes was similar in IBS and controls. However, there was a greater frequency of the low producer of IL-10 in those subjects with IBS-D, suggesting a genetic predisposition to abnormal immune regulation due to a lower anti-inflammatory cytokines IL10 in this subgroup.
Cytokine imbalance in irritable bowel syndrome: a systematic review and meta-analysis.
Abstract BACKGROUND: Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder of unknown etiology; although infection and inflammation have recently been considered as important etiologic agents. A recent meta-analysis showed correlations between cytokine [interleukin-10 (IL-10) and tumor necrosis factor (TNF)] gene polymorphisms and IBS; however, it is still unknown whether patients with IBS have different cytokine profiles compared to healthy population. METHODS: To determine the relationships between serum/plasma levels or mucosal expression of IL-10/TNF-α and IBS, we conducted a systematic review and meta-analysis based on case-control studies retrieved from PubMed and EMBASE search through August 2013. Standardized mean difference (SMD) was generated by using the inverse variance method. Heterogeneity was assessed based on I(2) values. KEY RESULTS: Serum/plasma levels of TNF-α tended to be higher in IBS vs controls (p = 0.09); this reached significance in IBS subtypes vs controls and in female patients with IBS. However, serum/plasma levels of IL-10 were not significantly different in IBS patients vs controls. Further analysis of serum/plasma IL-10 levels in IBS subtypes did not show any difference; however, analysis based on gender showed a significantly lower serum/plasma IL-10 levels in male patients with IBS vs male controls (p = 0.02). Colonic IL-10 mRNA had a significantly lower expression in IBS vs control (p = 0.001). CONCLUSIONS & INFERENCES: There is an imbalance of proinflammatory TNF-α, and anti-inflammatory IL-10, cytokines in IBS. Stratifying IBS patients based on cytokine profile may represent an opportunity for personalized treatment of this condition.
IL-10 and TNF-α polymorphisms in subjects with irritable bowel syndrome in Mexico
Revista Espanola De Enfermedades Digestivas, 2013
Background: there has been recent evidence of an alteration in irritable bowel syndrome (IBS) immune regulation, as well as variations in cytokine polymorphisms. Aims: to determine the frequency of the IL-10 (-1082G/A) and TNF-α (-308G/A) polymorphisms in subjects with IBS in Mexico. Methods: volunteers answered the Rome II Questionnaire and were classified as IBS (n = 45) and controls (n = 92). The IBS subjects were then categorized as IBS-D: 22.2 %, IBS-C: 28.9 %, and IBS-A/M: 48.9 %. The polymorphism frequency among groups was compared. Results: there were no differences between IBS vs. controls in the frequency of the high (8.9 vs. 18.5 %), intermediate (60.0 vs. 57.6 %), or low (23.9 vs. 38.9 %) producer IL-10 genotypes, p = 0.315. Neither were there differences in the high (0 vs. 1.1 %), intermediate (55.4 vs. 43.2 %), or low (43.5 vs. 56.8 %) producer TNF-α genotypes, p = 0.296. However the low producer of IL-10 was more frequent in IBS-D vs. IBS-C vs. IBS-A/M (63.6 vs. 7.1 vs. 33,3 %) p = 0.023. Conclusions: in this group of volunteers in Mexico, the frequency of the IL-10 (-1082G/A) and TNF-α (-308G/A) genotypes was similar in IBS and controls. However, there was a greater frequency of the low producer of IL-10 in those subjects with IBS-D, suggesting a genetic predisposition to abnormal immune regulation due to a lower anti-inflammatory component in this subgroup.
IL-10 and TNF-α polymorphisms in subjects with irritable bowel syndrome in Mexico
Revista Española de Enfermedades Digestivas, 2013
Background: there has been recent evidence of an alteration in irritable bowel syndrome (IBS) immune regulation, as well as variations in cytokine polymorphisms. Aims: to determine the frequency of the IL-10 (-1082G/A) and TNF-α (-308G/A) polymorphisms in subjects with IBS in Mexico. Methods: volunteers answered the Rome II Questionnaire and were classified as IBS (n = 45) and controls (n = 92). The IBS subjects were then categorized as IBS-D: 22.2 %, IBS-C: 28.9 %, and IBS-A/M: 48.9 %. The polymorphism frequency among groups was compared. Results: there were no differences between IBS vs. controls in the frequency of the high (8.9 vs. 18.5 %), intermediate (60.0 vs. 57.6 %), or low (23.9 vs. 38.9 %) producer IL-10 genotypes, p = 0.315. Neither were there differences in the high (0 vs. 1.1 %), intermediate (55.4 vs. 43.2 %), or low (43.5 vs. 56.8 %) producer TNF-α genotypes, p = 0.296. However the low producer of IL-10 was more frequent in IBS-D vs. IBS-C vs. IBS-A/M (63.6 vs. 7.1 vs. 33,3 %) p = 0.023. Conclusions: in this group of volunteers in Mexico, the frequency of the IL-10 (-1082G/A) and TNF-α (-308G/A) genotypes was similar in IBS and controls. However, there was a greater frequency of the low producer of IL-10 in those subjects with IBS-D, suggesting a genetic predisposition to abnormal immune regulation due to a lower anti-inflammatory component in this subgroup.
Proinflammatory Cytokine Gene Polymorphisms in Irritable Bowel Syndrome
Journal of Clinical Immunology, 2010
Introduction Irritable bowel syndrome (IBS) is a multifactorial functional gastrointestinal disorder, characterized by recurrent abdominal pain and altered bowel habits. Proinflammatory cytokines can play an important role in intestinal inflammation, while their production is under genetic control. Methods This study was performed in a group of patients with IBS to analyze the genotype frequencies of a number polymorphic genes coding for proinflammatory cytokine (interleukin-6 (IL), tumor necrosis factor-alpha (TNF-α), and IL-1 group). Using polymerase chain reaction with sequence-specific primers method, the cytokine genes were amplified, and alleles and genotypes of 71 patients with IBS were detected on gel electrophoresis, and the results were compared with healthy control subjects. Results Results of the analyzed data showed that the frequencies IL-1R C allele at position Pst-I 1970 (P = 0.017), IL-6 G allele at position −174 (P = 0.002), and TNF-α G allele at position −238 (P < 0.001) in the patient group were significantly higher than the control group. IL-6 GG genotype (−174) and TNF-α GG genotype (−238) in the patient group were also significantly overrepresented (P < 0.001), while IL-6 CG genotype (−174) and TNF-α GA genotype (−238) were significantly decreased in the patients with IBS (P < 0.001). The frequencies of IL-6 (−174, nt565) GG haplotype and TNF-α (−308, −238) GG haplotype were also significantly higher in the patient group (P < 0.001), whereas the frequencies of the haplotypes IL-6 CG and TNF-α GA were significantly decreased in the patients with IBS (P < 0.001). Conclusion IL-6 and TNF-alpha proinflammatory cytokine gene polymorphisms could change individual susceptibility to IBS and might have a role in pathophysiology of disease.
Interleukin-8 and -10 gene polymorphisms in irritable bowel syndrome
Molecular Biology Reports, 2012
Irritable bowel syndrome (IBS) is one of the most common gastrointestinal diagnoses seen by primary care providers and gastroenterologists. Proinflammatory cytokines interleukin (IL)-6 and IL-8 have been found increased in IBS patients. Cytokine gene single nucleotide polymorphisms (SNPs) of IL-8 and IL-10 have not been assessed in Mexican IBS patients. DNA was extracted from peripheral blood leucocytes of 45 IBS unrelated patients and 137 controls. Allele, genotype, and haplotype frequencies were determined by analyzing SNPs of IL-8 and IL-10 genes. IL-8 ? 396 G allele (P = 0.02), IL-8 ? 396(G/G) and IL-8 ? 781(C/T) genotypes (P \ 0.001), IL-10-1082A allele and IL-10-1082(A/A) genotype (P \ 0.001) were significantly increased in the IBS group. Haplotypes IL-8 ATCC (P = 0.03) and IL-10 ACC (P \ 0.001) were associated with susceptibility to develop IBS. An association of certain polymorphisms of IL-8 and IL-10 in IBS patients compared to controls was demonstrated, suggesting a role of these cytokine SNPs in the pathophysiology of IBS.
Digestive diseases and sciences, 2001
Interleukin-10 (IL-10) has a key role in regulating mucosal inflammation. The role of functional polymorphisms at positions -627 and -1117 in the IL-10 gene as candidate susceptibility loci in inflammatory bowel disease and their importance in determining disease extent were evaluated in 159 patients with ulcerative colitis (83 left-sided; 76 extensive), 90 patients with Crohn's disease (22 small bowel; 29 large bowel; 39 both), and 227 controls. Genotyping was performed either by PCR-RFLP assays (-627 site) or SSCP analysis (-1117 site). An excess of -627A allele was observed in patients with left-sided colitis (52%) compared with controls (33%; P = 0.004) suggesting that IL-10 may influence the extent of the disease. These results were not replicated in a newly recruited group (N = 100) of patients with UC. We conclude that polymorphisms at -627 and -1117 sites in the IL-10 gene do not contribute to the susceptibility to IBD or determining the extent of the disease in our popu...