Dataset Information

Protective association of TNFSF15 polymorphisms with Crohn's disease and ulcerative colitis: A meta-analysis.

ABSTRACT: Background/Aims:Three extensively investigated polymorphisms (rs3810936, rs7848647, and rs6478108) in tumor necrosis factor super family member 15 (TNFSF15) gene have been implicated in risk for inflammatory bowel disease (IBD). We performed a quantitative synthesis of the evidence to clarify these associations of TNFSF15 polymorphisms with IBD. Materials and Methods:Data were extracted from PubMed and EMBASE, up to March 15, 2018. Meta-analysis was performed by critically reviewing five studies for rs3810936 polymorphism (2251 cases and 2442 controls), four studies for rs7848647 polymorphism (1503 cases and 1816 controls), and four studies for rs6478108 polymorphism (1502 cases and 1817 controls). Results:Our analysis suggested that rs3810936 polymorphism was significantly associated with decreased risk of Crohn's disease (CD) and ulcerative colitis (UC). For rs7848647 polymorphism, significantly protective association between this polymorphism and CD risk was also observed, but not in UC. For rs6478108 polymorphism, we also detected a significantly protective association with CD risk in all genetic model but not in UC. Conclusions:This meta-analysis suggests that TNFSF15 polymorphisms may contribute to genetic susceptibility of IBD.

SUBMITTER: He L

PROVIDER: S-EPMC6080154 | biostudies-literature | 2018 Jul-Aug

REPOSITORIES: biostudies-literature

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Protective association of TNFSF15 polymorphisms with Crohn's disease and ulcerative colitis: A meta-analysis.

He Liwen L Chen Jiamin J Sun Jiachen J Peng Junsheng J He Qing Q

Saudi journal of gastroenterology : official journal of the Saudi Gastroenterology Association 20180701 4

<h4>Background/aims</h4>Three extensively investigated polymorphisms (rs3810936, rs7848647, and rs6478108) in tumor necrosis factor super family member 15 (TNFSF15) gene have been implicated in risk for inflammatory bowel disease (IBD). We performed a quantitative synthesis of the evidence to clarify these associations of TNFSF15 polymorphisms with IBD.<h4>Materials and methods</h4>Data were extracted from PubMed and EMBASE, up to March 15, 2018. Meta-analysis was performed by critically reviewi ...[more]

PMID: 29873318

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Project description:BackgroundMany 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 methodsElectronic 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.ResultsTwelve 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).ConclusionThis meta-analysis indicates that carriers of the STAT3 rs744166 'A' allele have a significantly greater risk of CD and UC, especially among Caucasians.

Project description:BackgroundAlthough electronic health interventions are considered safe and efficient, evidence regarding the cost-effectiveness of telemonitoring in inflammatory bowel disease is lacking.ObjectiveWe aimed to evaluate the cost-effectiveness and cost-utility of the Telemonitorización de la Enfermedad de Crohn y Colitis Ulcerosa (Telemonitoring of Crohn's Disease and Ulcerative Colitis [TECCU]) Web platform (G_TECCU intervention group) for telemonitoring complex inflammatory bowel disease, compared with standard care (G_control) and nurse-assisted telephone care (G_NT intervention group).MethodsWe analyzed cost-effectiveness from a societal perspective by comparing the 3 follow-up methods used in a previous 24-week randomized controlled trial, conducted at a tertiary university hospital in Spain. Patients with inflammatory bowel disease who initiated immunosuppressants or biologic agents, or both, to control inflammatory activity were recruited consecutively. Data on the effects on disease activity (using clinical indexes) and quality-adjusted life-years (using the EuroQol 5 dimensions questionnaire) were collected. We calculated the costs of health care, equipment, and patients' productivity and social activity impairment. We compared the mean costs per patient, utilities, and bootstrapped differences.ResultsWe included 63 patients (21 patients per group). TECCU saved €1005 (US $1100) per additional patient in remission compared with G_control (95% CI €-13,518 to 3137; US $-14,798 to 3434), with a 79.96% probability of being more effective at lower costs. Compared with G_NT, TECCU saved €2250 (US $2463) per additional patient in remission (95% CI €-15,363 to 11,086; US $-16,817 to 12,135), and G_NT saved €538 (US $589) compared with G_control (95% CI €-6475 to 5303; US $-7088 to 5805). G_TECCU and G_NT showed an 84% and 67% probability, respectively, of producing a cost saving per additional quality-adjusted life-year (QALY) compared with G_control, considering those simulations that involved negative incremental QALYs as well.ConclusionsThere is a high probability that the TECCU Web platform is more cost-effective than standard and telephone care in the short term. Further research considering larger cohorts and longer time horizons is required.Trial registrationClinicalTrials.gov NCT02943538; https://clinicaltrials.gov/ct2/show/NCT02943538 (http://www. webcitation.org/746CRRtDN).

Project description:BackgroundCrohn's disease and ulcerative colitis are the two major forms of inflammatory bowel disease; treatment strategies have historically been determined by this binary categorisation. Genetic studies have identified 163 susceptibility loci for inflammatory bowel disease, mostly shared between Crohn's disease and ulcerative colitis. We undertook the largest genotype association study, to date, in widely used clinical subphenotypes of inflammatory bowel disease with the goal of further understanding the biological relations between diseases.MethodsThis study included patients from 49 centres in 16 countries in Europe, North America, and Australasia. We applied the Montreal classification system of inflammatory bowel disease subphenotypes to 34,819 patients (19,713 with Crohn's disease, 14,683 with ulcerative colitis) genotyped on the Immunochip array. We tested for genotype-phenotype associations across 156,154 genetic variants. We generated genetic risk scores by combining information from all known inflammatory bowel disease associations to summarise the total load of genetic risk for a particular phenotype. We used these risk scores to test the hypothesis that colonic Crohn's disease, ileal Crohn's disease, and ulcerative colitis are all genetically distinct from each other, and to attempt to identify patients with a mismatch between clinical diagnosis and genetic risk profile.FindingsAfter quality control, the primary analysis included 29,838 patients (16,902 with Crohn's disease, 12,597 with ulcerative colitis). Three loci (NOD2, MHC, and MST1 3p21) were associated with subphenotypes of inflammatory bowel disease, mainly disease location (essentially fixed over time; median follow-up of 10·5 years). Little or no genetic association with disease behaviour (which changed dramatically over time) remained after conditioning on disease location and age at onset. The genetic risk score representing all known risk alleles for inflammatory bowel disease showed strong association with disease subphenotype (p=1·65 × 10(-78)), even after exclusion of NOD2, MHC, and 3p21 (p=9·23 × 10(-18)). Predictive models based on the genetic risk score strongly distinguished colonic from ileal Crohn's disease. Our genetic risk score could also identify a small number of patients with discrepant genetic risk profiles who were significantly more likely to have a revised diagnosis after follow-up (p=6·8 × 10(-4)).InterpretationOur data support a continuum of disorders within inflammatory bowel disease, much better explained by three groups (ileal Crohn's disease, colonic Crohn's disease, and ulcerative colitis) than by Crohn's disease and ulcerative colitis as currently defined. Disease location is an intrinsic aspect of a patient's disease, in part genetically determined, and the major driver to changes in disease behaviour over time.FundingInternational Inflammatory Bowel Disease Genetics Consortium members funding sources (see Acknowledgments for full list).

Dataset Information

Protective association of TNFSF15 polymorphisms with Crohn's disease and ulcerative colitis: A meta-analysis.

Publications

Protective association of TNFSF15 polymorphisms with Crohn's disease and ulcerative colitis: A meta-analysis.

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