RESUMO
OBJECTIVE: To determine a family aggregation pattern of Irritable Bowel Syndrome (IBS). DESIGN: it is a case-control study with a 1.2 ratio. SETTING: External consultation of a general family medicine practice. PARTICIPANTS: men and women from 18 to 60 years old. Cases (40): people with IBS according to the Rome IV criteria, and Controls (80): relatives without gastrointestinal disease. MAIN MEASUREMENTS: Sociodemographic variables, related stressful events, predominant evacuation patterns, and family repetition patterns for IBS. Data were analyzed with descriptive and inferential statistics. Chi-square for categorical data (< p.05 as significant) estimate of ORs with 95% confidence interval. The institutional ethics committee approved it. RESULTS: The IBS presentation pattern was repeated in relatives, mainly first-degree. The risk of suffering from IBS was higher when the father reported it (OR 11.2 (95% CI; 1.2 -100.1), than the mother OR 3,7 (95% CI; 1.4 - 9.9), sibling OR 2.8 (95% CI; 1.1 - 6.6. In both groups, the relative who most frequently presented IBS was in the collateral line (sibling) (37.5% in cases vs. 17.5% in controls (p=0.023). In both groups, the predominant gender was female, with 80. 0% in cases and 57.5% in controls. CONCLUSION: SII has a familial recurrence pattern in the Mexican population. The disease is more frequent in first-degree relatives. It is important to elucidate the importance of the role that plays genetic background vs. the influence of the family environment in SII.
Assuntos
Síndrome do Intestino Irritável , Masculino , Humanos , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Síndrome do Intestino Irritável/epidemiologia , Síndrome do Intestino Irritável/genética , Estudos de Casos e Controles , Mães , Encaminhamento e Consulta , Inquéritos e QuestionáriosRESUMO
Irritable bowel syndrome (IBS) is a common chronic functional gastrointestinal disorder defined by disturbances in bowel habits and abdominal pain, in the absence of known organic pathology that affects between 5 to 10% of healthy populations. Despite improvements in detection and treatment, the pathogenesis of IBS has not been clarified. Several microRNAs (miRNAs) are involved in the pathogenesis of IBS through increased intestinal permeability, inflammation, and modulation of visceral hyperalgesia, and they may have the potential to be used as biomarkers and therapeutic targets. Here, we have summarized the recent advances about the role of miRNAs in the development of IBS symptoms and the possibility to use them as therapeutic targets to mitigate symptoms in IBS.
Assuntos
Síndrome do Intestino Irritável , MicroRNAs , Humanos , Síndrome do Intestino Irritável/diagnóstico , Síndrome do Intestino Irritável/genética , Síndrome do Intestino Irritável/terapia , MicroRNAs/genética , Intestinos , Hiperalgesia/complicações , InflamaçãoRESUMO
MicroRNAs (miRNAs) are tiny (20-24 nucleotides long), non-coding, highly conserved RNA molecules that play a crucial role within the post-transcriptional regulation of gene expression via sequence-specific mechanisms. Since the miRNA transcriptome is involved in multiple molecular processes needed for cellular homeostasis, its altered expression can trigger the development and progression of several human pathologies. In this context, over the last few years, several relevant studies have demonstrated that dysregulated miRNAs affect a wide range of molecular mechanisms associated with irritable bowel syndrome (IBS), a common gastrointestinal disorder. For instance, abnormal miRNA expression in IBS patients is related to the alteration of intestinal permeability, visceral hyperalgesia, inflammatory pathways, and pain sensitivity. Besides, specific miRNAs are differentially expressed in the different subtypes of IBS, and therefore, they might be used as biomarkers for precise diagnosis of these pathological conditions. Accordingly, miRNAs have noteworthy potential as theragnostic targets for IBS. Hence, in this current review, we present an overview of the recent discoveries regarding the clinical relevance of miRNAs in IBS, which might be useful in the future for the development of miRNA-based drugs against this disorder.
Assuntos
Síndrome do Intestino Irritável , MicroRNAs , Humanos , MicroRNAs/genética , Síndrome do Intestino Irritável/diagnóstico , Síndrome do Intestino Irritável/genética , Síndrome do Intestino Irritável/complicações , Regulação da Expressão Gênica , Limiar da Dor , HiperalgesiaRESUMO
Irritable bowel syndrome (IBS) is the most frequent functional gastrointestinal disorder, worldwide, with a high prevalence among Mestizo Latin Americans. Because several inflammatory disorders appear to affect this population, a further understanding of host genomic background variants, in conjunction with colonic mucosa dysbiosis, is necessary to determine IBS physiopathology and the effects of environmental pressures. Using a simple polygenic model, host single nucleotide polymorphisms (SNPs) and the taxonomic compositions of microbiota were compared between IBS patients and healthy subjects. As proof of concept, five IBS-Rome III patients and five healthy controls (HCs) were systematically studied. The human and bacterial intestinal metagenome of each subject was taxonomically annotated and screened for previously annotated IBS, ulcerative colitis, and Crohn's disease-associated SNPs or taxon abundance. Dietary data and fecal markers were collected and associated with the intestinal microbiome. However, more than 1,000 variants were found, and at least 76 SNPs differentiated IBS patients from HCs, as did associations with 4 phyla and 10 bacterial genera. In this study, we found elements supporting a polygenic background, with frequent variants, among the Mestizo population, and the colonic mucosal enrichment of Bacteroides, Alteromonas, Neisseria, Streptococcus, and Microbacterium, may serve as a hallmark for IBS.
Assuntos
Bactérias/classificação , Colo/microbiologia , Etnicidade , Microbioma Gastrointestinal , Síndrome do Intestino Irritável/genética , Síndrome do Intestino Irritável/microbiologia , Herança Multifatorial , Adulto , Bactérias/genética , Encéfalo/metabolismo , Dieta , Etnicidade/genética , Fezes/microbiologia , Feminino , Frequência do Gene , Humanos , Imunidade/genética , Mucosa Intestinal/microbiologia , Masculino , Metagenoma , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Adulto JovemRESUMO
Irritable Bowel Syndrome (IBS) is a functional disorder characterized by abdominal discomfort associated with changes in bowel habit and increased intestinal sensitivity. It is one of the most common disorders of digestive health in Chile as well as in the world. Although the pathophysiological mechanisms of IBS have yet to be fully established, it is known that (epi-) genetic factors are involved in the development of the disorder. Bcl3 (B-cell leukemia/lymphoma 3) is a regulatory protein of the intestinal inflammatory response, specifically, with regard to the signaling pathways of NF-kB (Nuclear Factor-kB). Among the variability of the human genome, the gene encoding Bcl3 contains the polymorphism SNPs rs2927488 (variants A/G) which has been associated with susceptibility to developing Inflammatory Bowel Disease (IBD). Furthermore, the presence of this polymorphic variant has been correlated with increased levels of Bcl3 gene expression in patients with Crohns Disease. Our laboratory is focused on understanding the potential relationship between Bcl3 and IBS. Our preliminary studies describe an increased expression of Bcl3 at the intestinal mucosal epithelium in IBS patients with a diarrheal-phenotype (IBS-D). We are now interested to investigate if the presence of the variant SNP rs2927488(A/G) is a susceptibility factor for IBS development and to understand the significance of its relationship with Bcl3 expression, in Chilean IBS patients. In this review, we focus primarily on the relationship between rs2927488(A/G) polymorphism of Bcl3 gene, its protein expression and its mechanisms of control over the inflammatory response...
Assuntos
Humanos , Polimorfismo Genético , Síndrome do Intestino Irritável/epidemiologia , Síndrome do Intestino Irritável/fisiopatologia , Síndrome do Intestino Irritável/genéticaRESUMO
We examined patients of Han nationality diagnosed with irritable bowel syndrome with diarrhea (IBS-D) in Guangdong, China, to analyze the correlation between DQB1 allele polymorphisms and the genetic susceptibility to IBS-D. A total of 120 IBS-D patients of Han nationality in Guangdong, China, and 60 healthy control volunteers were included. DQB1 allele polymorphisms were investigated by polymerase chain reaction. Subjects' serum interleukin (IL)-10 level, colonic permeability, and tight junction marker zonula occludens 1 (ZO1) mRNA level were also investigated. Our data showed that the DQB1*02 allele frequency was significantly higher in IBS-D patients, while the DQB1*0603 frequency was lower than in healthy volunteers. The DQB1*03, DQB1*04, DQB1*05, DQB1*0601, DQB1*0602, and DQB1*0604 alleles did not show significant differences between IBS-D patients and healthy controls. Furthermore, patients with DQB1*03- positive and DQB1*0603-negative alleles showed more severe colonic permeability and lower serum IL-10 level and ZO1 level compared to healthy controls or even IBS-D patients with other genotypes. The present study indicated the DQB1*02 or DQB1*0603 alleles are related to IBS-D occurrence in Guangdong, China, and the mechanism of the disease may be related to reduced serum IL-10 levels.
Assuntos
Povo Asiático/genética , Diarreia/complicações , Diarreia/genética , Cadeias beta de HLA-DQ/genética , Interleucina-10/sangue , Síndrome do Intestino Irritável/genética , Adulto , Estudos de Casos e Controles , China , Colo/fisiopatologia , Diarreia/fisiopatologia , Feminino , Predisposição Genética para Doença , Humanos , Síndrome do Intestino Irritável/fisiopatologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Adulto Jovem , Proteína da Zônula de Oclusão-1/genéticaRESUMO
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-alpha (-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-alpha 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-alpha (-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.
Assuntos
Interleucina-10/genética , Síndrome do Intestino Irritável/genética , Polimorfismo Genético , Fator de Necrose Tumoral alfa/genética , Adulto , Feminino , Humanos , Masculino , MéxicoRESUMO
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.
Assuntos
Interleucina-10/genética , Interleucina-8/genética , Síndrome do Intestino Irritável/genética , Polimorfismo de Nucleotídeo Único , Adulto , Alelos , Estudos de Casos e Controles , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
In recent times, some common "non-pathogenic" parasites, such as Blastocystis and Dientamoeba fragilis, have been associated to the aetiology of irritable bowel syndrome (IBS), while host pro-inflammatory cytokine gene polymorphisms might have a role in the pathophysiology of the disease. Therefore, Blastocystis subtypes (ST), D. fragilis and gene promoter single nucleotide polymorphisms of interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) in IBS patients and controls were studied. After giving written consent, 45 patients with symptoms of IBS according to the Rome III criteria and 45 controls were enrolled. DNA was extracted from peripheral blood for SNP analysis at position -174 for IL-6 as well as -238 and -308 for TNF-α. Blastocystis was more common in the IBS group (p = 0.043). Interestingly, D. fragilis was found more frequently in the control group (p = 0.002); Blastocystis ST1 and 3 were most frequent in both groups. Haploview analysis revealed linkage disequilibrium in TNF-α (p < 0.0001); however, none of the SNPs for IL-6 and TNF-α were found to be significantly related with IBS. The clinical and molecular approaches undertaken for the first time in Latin American IBS patients demonstrated an association with Blastocystis that supports a pathogenic role of this parasite in IBS Furthermore, co-infections with ST1 and ST3 were frequent; thus, the genetic diversity proposed within ST polymorphisms does not rule out that particular strains might be associated with disease. In addition, our results do not support a major contribution of IL-6 and TNF-α gene polymorphisms in the susceptibility to IBS.