Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021390 (inflammatory bowel disease)
 23,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Association between single nucleotide polymorphisms (SNPs) within the MYO9B gene and celiac disease was recently reported. The role of MYO9B in celiac disease was suggested to relate to an epithelial barrier defect. The region to which MYO9B localize is also linked with inflammatory bowel disease (IBD). For these reasons, we hypothesize that MYO9B could also be a susceptibility gene in IBD. To address this, we performed an association study of a Norwegian IBD cohort (149 patients with Crohn's disease, 308 patients with ulcerative colitis and 562 healthy controls) using SNPs, which tagged the celiac disease associated MYO9B haplotype. No association between these SNPs and IBD was observed. Our results failed to support the notion that MYO9B is a susceptibility gene in IBD.
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PMID:Association analysis of MYO9B gene polymorphisms and inflammatory bowel disease in a Norwegian cohort. 1694 47

To date, seven studies have provided evidence for an association between the gene encoding for myosin IXB (MYO9B) and celiac disease (CD), and inflammatory bowel diseases, including single nucleotide polymorphisms (SNPs) rs2305767, rs1457092, and rs2305764. We investigated whether MYO9B is associated with T1D. The three SNPs were genotyped in Dutch samples from 288 T1D patients and 1615 controls. The A allele of SNP rs2305767A>G showed some evidence of association with T1D (nominal p for genotype = 0.06; OR carrier = 1.51, 95% CI = 1.04-2.19), but not in British samples from 4301 case patients and 4706 controls (p = 0.53), or when the Dutch and UK data were pooled (N patients = 4582, N controls= 6224; Mantel-Hansel p = 0.83). Furthermore, the nonsynonymous rs1545620 C>A SNP that has been associated with the inflammatory bowel disease, showed no association with T1D in British case-control set (p = 0.57). We conclude that MYO9B might not be a strong determinant of T1D, although there was some association in our initial Dutch study. Further studies are needed to evaluate the role of MYO9B in T1D.
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PMID:Association analysis of myosin IXB and type 1 diabetes. 2030 73

Over the last 10 years, sensitive advancement has been made in the study of genetic susceptibility to inflammatory bowel disease (IBD). Complementary methodologies of linkage, fine-mapping and candidate-gene studies have led to the identification of a number of susceptibility genes and loci, including caspase activation and recruitment domain 15 (CARD15), major histocompatibility complex (MHC) and IBD5, whereas many other genes (nucleotide oligomerization domain 1 [NOD1], tumor-upregulated CARD-containing antagonist of caspase-9 [TUCAN], Toll-like receptors [TLR], interleukin 23 receptor [IL23R], multidrug resistance 1 [MDR1], myosin IXb [MYO9B], chemokine [C-Cmotif] ligand 20 [CCL20], human beta-defensin 2 [HBD-2], autophagy-related 16-like 1 [ATG16L1]) are still awaiting confirmation. The CARD15 gene is currently the most widely replicated and investigated gene. The exact sequence of events that link CARD15 variants to early pathogenetic changes is unknown. However, the role of the encoded protein confirms the relevance of appropriate responses by the innate immune system to intestinal bacteria, including the production of antimicrobial peptides (defensins). With the implementation of new genomics and proteomics methodologies, genetic research will advance our further understanding of the clinical heterogeneity of IBD and tackle the complex interactions between genetic and environmental risk factors.
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PMID:Dissecting genetic predisposition to inflammatory bowel disease: current progress and prospective application. 2047 73

Various genes that may influence the intestinal barrier have been identified, including MAGI2, PARD3, and MYO9B. These genes are associated with inflammatory bowel disease (IBD) in several European studies. A total of 2,049 individuals (656 Crohn's disease [CD], 544 ulcerative colitis [UC], and 849 controls) were genotyped and association studies were performed for 1 single nucleotide polymorphism (SNP) in MAGI2, 1 SNP in PARD3, and 6 SNPs in MYO9B. We reported an association between 3 SNPs in MYO9B and ileal involvement with rs1457092 as the most significant SNP (p = 0.0073, odds ratio [OR] 0.69 [95% confidence interval (95% CI) 0.52-0.90]). The nonsynonymous SNP rs1545620 exhibited a p value of 0.014, OR 0.72 (95% CI 0.55-0.93). MYO9B was not associated with UC. MAGI2 or PARD3 was not associated with IBD. A 6-SNP haplotype block in MYO9B demonstrated association with CD and ileal CD (p = 0.0030 and 0.0065, respectively). These data demonstrate an association of MYO9B with ileal CD; however, there was no association of MAGI2 and PARD3 with IBD. Because the direction of association of MYO9B in this Canadian study was not consistent with European studies, further studies are needed to elucidate the role of MYO9B in IBD.
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PMID:Replication of genetic variation in the MYO9B gene in Crohn's disease. 2151 26

Genetic studies have implicated MYO9B, which encodes myosin IXb (Myo9b), a motor protein with a Rho GTPase activating domain (RhoGAP), as a susceptibility gene for inflammatory bowel disease (IBD). Moreover, we have recently shown that knockdown of Myo9b in an intestinal epithelial cell line impairs wound healing and barrier function. Here, we investigated whether mice lacking Myo9b have impaired intestinal barrier function and features of IBD. Myo9b knock out (KO) mice exhibit impaired weight gain and fecal occult blood (indicator of gastrointestinal bleeding), and increased intestinal epithelial cell apoptosis could be detected along the entire intestinal axis. Histologic analysis revealed intestinal mucosal damage, most consistently observed in the ileum, which included superficial ulceration and neutrophil infiltration. Focal lesions contained neutrophils and ultrastructural examination confirmed epithelial discontinuity and the deposition of extracellular matrix. We also observed impaired mucosal barrier function in KO mice. Transepithelial electrical resistance of KO ileum is >3 fold less than WT ileum. The intestinal mucosa is also permeable to high molecular weight dextran, presumably due to the presence of mucosal surface ulcerations. There is loss of tight junction-associated ZO-1, decreased lateral membrane associated E-cadherin, and loss of terminal web associated cytokeratin filaments. Consistent with increased Rho activity in the KO, there is increased subapical expression of activated myosin II (Myo2) based on localization of phosphorylated Myo2 regulatory light chain. Except for a delay in disease onset in the KO, no difference in dextran sulfate sodium-induced colitis and lethality was observed between wild-type and Myo9b KO mice.
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PMID:Mice lacking myosin IXb, an inflammatory bowel disease susceptibility gene, have impaired intestinal barrier function and superficial ulceration in the ileum. 2697 22

Myosin IXB (MYO9B) gene polymorphisms have been extensively investigated in terms of their associations with inflammatory bowel disease (IBD), with contradictory results. The aim of this meta-analysis was to evaluate associations between MY09B gene polymorphisms and the risk of IBD, Crohn's disease (CD) and ulcerative colitis (UC). Eligible studies from PubMed, Embase, and CNKI databases were identified. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. Ten studies published in eight papers reporting 8,975 cases and 9,482 controls were included in this meta-analysis. Five MY09B gene polymorphisms were evaluated: rs1545620, rs962917, rs1457092, rs2305764, and rs2305767. Our data suggested that the rs1545620 polymorphism was associated with a decreased risk of IBD. A similar result was found for rs2305767 and UC. The rs962917 single nucleotide polymorphism (SNP) increased the risk of IBD, CD and UC. Moreover, rs1457092 increased the risk of IBD and UC. Rs2305764 was also associated with an increased risk of IBD. Furthermore, stratification analyses indicated that rs1545620 decreased the risk of IBD, while rs962917 increased the risk of IBD, CD and UC in Caucasian populations. To sum up, our data indicate that these five SNPs in MY09B are significantly associated with the risk of IBD.
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PMID:MYO9B gene polymorphisms are associated with the risk of inflammatory bowel diseases. 2755 56