The genetics of inflammatory bowel disease.

Inflammatory Bowel Disease Center, Section of Digestive Diseases, Yale University, New Haven, Connecticut 06520-8019, USA.
Gastroenterology (Impact Factor: 13.93). 11/2007; 133(4):1327-39. DOI: 10.1053/j.gastro.2007.08.032
Source: PubMed
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    ABSTRACT: PurposeWhether patients with inflammatory bowel disease (IBD) exhibit a high risk of developing varicella zoster virus (VZV) infection in Asian populations remains inconclusive. We investigated the causal relationship between two diseases by analysing the Taiwan National Health Insurance Research Database.Patients and methodsBased on a universal insurance claims database, we enrolled 7055 IBD patients and 28,220 age- and sex-matched controls. We calculated the hazard ratios (HRs) and 95% confidence intervals (CIs) of the herpes zoster virus (HZV) in the IBD and comparison cohorts, using the Cox proportional hazards regression model.ResultsPatients with IBD exhibited significantly higher risk of the HZV compared with the controls (adjusted HRs, 1.42; 95% CI, 1.27–1.60). Further analysis indicated that male patients (adjusted HRs, 1.61; 95% CI, 1.35–1.92), aged 35–44 (adjusted HRs, 1.47; 95% CI, 1.08–2.01) and aged 65 years and older (adjusted HRs, 1.47; 95% CI, 1.19–1.80), and patients without comorbidities (adjusted HRs, 1.44; 95% CI, 1.26–1.66), exhibited excessive risks of VZV infection. Moreover, our findings show that the overall risk of developing VZV infection increased risk from 1.03 (95% CI, 0.90–1.18) (≤ 2 visits) to 9.76 (95% CI, 7.60–12.5) (> 4 visits), which correlates positively with the frequency of medical visits (trend test p < 0.0001).Conclusion Patients with IBD, particularly men aged 35–44/65 years and over, and patients without comorbidities, are associated with a long-term risk of VZV infection. The excessive risk of VZV infection should be considered for administering vaccines to IBD patients.
    International Journal of Clinical Practice 10/2014; DOI:10.1111/ijcp.12508 · 2.54 Impact Factor
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    ABSTRACT: Background Many studies have investigated the associations between the signal transducer and activator of transcription 3 (STAT3) in the susceptibility to ulcerative colitis (UC) and Crohn's disease (CD). However, the results remain inconsistent. This meta-analysis determined the risk of STAT3 rs744166 polymorphism-conferred UC and CD susceptibility. Materials and Methods Electronic databases, including PubMed, EMBASE and the Cochrane Library, were searched for all eligible studies that evaluated the association between STAT3 rs744166 polymorphisms with UC and CD risk up to August 21, 2014. The pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using fixed- or random-effects models. Results Twelve studies containing 10298 patients with CD, 4244 patients with UC and 11191 controls were included in this meta-analysis. The results indicated that the STAT3 rs744166 polymorphism was associated with CD and UC susceptibility (CD: GA+AA vs. GG, OR = 1.20, 95%CI, 1.11–1.30, I2 = 0%, Punadjusted<0.00001, PBonferroni<0.00005, PFDR<0.00001; UC: GA+AA vs. GG, OR = 1.21, 95%CI, 1.08–1.36, I2 = 1%, Punadjusted = 0.001, PBonferroni = 0.005, PFDR = 0.00125). In subgroup analyses by ethnicity, the significant association was found only among Caucasians. However, when grouped by age of onset, positive associations were found both among adults and children. In addition, when stratified by study design and genotyping methods, the risk of CD was significantly associated with the STAT3 rs744166 polymorphism in hospital-based and population-based groups and in SNP Array and SNPlex groups. For UC, significant associations were also found in population-based, PCR-RFLP and SNPlex groups. Moreover, these findings were sufficiently robust to withstand the Bonferroni correction and false discovery rate (FDR). Conclusion This meta-analysis indicates that carriers of the STAT3 rs744166 ‘A’ allele have a significantly greater risk of CD and UC, especially among Caucasians.
    Autoimmunity 07/2014; 9(10):1-7. DOI:10.3109/08916934.2014.930735 · 2.75 Impact Factor
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    ABSTRACT: Crohn's disease is a complex inherited disorder of unknown pathogenesis with environmental, genetic and microbial factors involved in the development of the disease. A remarkable feature of this disease in childhood is the effective response to exclusive enteral nutrition (EEN) therapy and the need for complete exclusion of normal diet required for success (principle of exclusivity). EEN or dietary interventions might act through removal of dietary components, which affect microbial composition, decrease a proinflammatory response and promote restitution of the epithelial barrier, likewise allowing termination of this vicious disease-forming cycle before a critical threshold is reached. Multiple traditional and nontraditional dietary components may affect the microbiome, mucous layer, intestinal permeability, or adherence and translocation of pathobionts. We review the epidemiological data, as well as data from animal models and cell lines, and propose a model for pathogenesis we have termed the 'bacterial penetration cycle', whereby dietary components such as animal fat, high sugar intake and gliadin, and consumption of emulsifiers, maltodextrin as well as low-fiber diets may be able to cause a localized acquired bacterial clearance defect, leading to bacterial adhesion and penetration, and subsequently inflammation in the gut. © 2014 S. Karger AG, Basel.
    Digestive Diseases 01/2014; 32(4):389-94. DOI:10.1159/000358143 · 1.83 Impact Factor