Risk Factor For Ulcerative Colitis Research Articles

Serum urate is associated with an increased risk of inflammatory bowel disease: A bidirectional Mendelian randomization study.

Previous studies have indicated bidirectional associations between urate levels and inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD). However, it remains unclear whether the observations are causal because of confounding factors. To investigate the causal associations between urate levels and IBD using bidirectional Mendelian randomization (MR). Independent genetic variants for urate levels and IBD were selected as instrumental variables from published genome-wide association studies (GWASs). Summary statistics for instrument-outcome associations were retrieved from three separate databases for IBD (the UK Biobank, the FinnGen database and a large GWAS meta-analysis) and one for urate levels (a large GWAS meta-analysis). MR analyses included the inverse-variance-weighted method, weighted-median estimator, MR-Egger and sensitivity analyses (MR-PRESSO). A meta-analysis was also conducted to merge the data from separate outcome databases using a fixed-effects model. Genetically higher serum urate levels were strongly associated with an increased risk of UC [odds ratio (OR): 1.95, 95% confidence interval (CI): 1.86-2.05] after outlier correction, and the ORs (95%CIs) for IBD and CD were 0.94 (95%CI: 0.86-1.03) and 0.91 (95%CI: 0.80-1.04), respectively. Animal studies have confirmed the positive association between urate levels and UC. Moreover, genetically predicted IBD was inversely related to urate levels (OR: 0.97, 95%CI: 0.94-0.99). However, no association was observed between genetically influenced UC or CD and urate levels. Urate levels might be risk factors for UC, whereas genetically predicted IBD was inversely associated with urate levels. These findings provide essential new insight for treating and preventing IBD.

APOL1 Induces Pyroptosis of Fibroblasts Through NLRP3/Caspase-1/GSDMD Signaling Pathway in Ulcerative Colitis.

Pyroptosis is a form of proinfammatory gasdermin-mediated programmed cell death. Abnormal infammation in the intestine is a critical risk factor for Ulcerative colitis (UC). However, at present, it is not clear whether pyroptosis of colonic fibroblasts is involved in the pathogenesis and progression of UC. In this study, key genes associated with UC were identified by bioinformatics analysis. Datasets were downloaded from the Gene Expression Omnibus (GEO) database (GSE193677). The differentially expressed genes were analyzed, and the hub genes were screened by weighted gene co-expression network analysis (WGCNA) and differentially expressed genes. We also downloaded the dataset from GEO for single-cell RNA sequencing (GSE231993). The expression of key genes was verified by immunohistochemistry, immunofluorescence and Western blot, and the specific pathways of key genes inducing pyroptosis in cell lines were explored. The results of bioinformatics analysis showed that the expression of APOL1 and CXCL1 in UC tissues was significantly higher than that in normal tissues. The results of single-cell analysis showed that the two genes were co-localized to fibroblasts. These results were consistent with the results of immunohistochemistry and immunofluorescence colocalization in human intestinal mucosa specimens. Furthermore, APOL1 overexpression induced NLRP3-caspase1-GSDMD-mediated pyroptosis of fibroblasts, which was confirmed by Western blot. APOL1 induces pyroptosis of fibroblasts mediated by NLRP3-Caspase1-GSDMD signaling pathway and promote the release of chemokines CXCL1. Fibroblasts may play a crucial role in the pathogenesis and progression of UC.

Dietary Management of Ulcerative Colitis: Case Report

Genetic makeup, gut microorganisms, autoimmunity and environmental factors are the major risk factors of ulcerative colitis; an inflammatory bowel disease. Because of its severe effects on nutritional status, this case was taken with an aim to improve the nutritional status; with dietary management. An 18 years old adolescent girl was presented to medicine ward of Sheikh Zayed Hospital Lahore with diagnosed ulcerative colitis and presently, she had the complaint of loose stools, nausea/vomiting, decreased appetite and micronutrient deficiencies. Patient’s regimen was formulated on the basis of all presenting complaints to overcome the worsening symptoms and to improve her nutritional status. Planned regimen helped patient in obtaining satisfactory results, her baseline markers and symptoms were compared with her latest ones for proper evaluation. In current case report, consumption of white bread, rice and tapioca pearls was recommended from bread and cereals and the consumption of whole grain or bran products was severely restricted. Use of fibrous vegetables or leafy vegetables was also restricted and the consumption of starchy vegetables was recommended to the patients from the vegetables group. Consumption of fruits without peel was recommended to patient; preferably to consume banana and apple sauce to prevent aggravation in gastrointestinal symptoms whereas the consumption of fruits with high fiber content was restricted. In current case study consumption of lactose free milk and yogurt was recommended to patient whereas consumption of lactose containing milk and milk products was restricted. Dietary management played a very significant role on her nutritional status; thus proper medical nutritional therapy along with lifestyle modification can help in managing ulcerative colitis.

Incidence and Risk Factors of Cancer in the Anal Transitional Zone and Ileal Pouch following Surgery for Ulcerative Colitis and Familial Adenomatous Polyposis.

Simple SummaryProctocolectomy with ileal pouch-anal anastomosis is the intervention of choice for ulcerative colitis and familial adenomatous polyposis requiring surgery. However high-grade dysplasia and cancer in the anal transitional zone and ileal pouch after 20 years is estimated to be 2 to 4.5% and 3 to 10% in ulcerative colitis and familial polyposis, respectively. The risk factors for ulcerative colitis are the presence of pre-operative dysplasia or cancer, disease duration > 10 years and severe villous atrophy. For familial polyposis, the risk factors are the number of pre-operative polyps > 1000, surgery with stapled anastomosis and the duration of follow-up. Even if anal transitional zone and ileal pouch cancers seldom occur following proctectomy for ulcerative colitis and familial adenomatous polyposis, the high mortality rate associated with this complication warrants close endoscopic monitoring, mainly every year with pouchoscopy including chromoendoscopy.Proctocolectomy with ileal pouch-anal anastomosis is the intervention of choice for ulcerative colitis and familial adenomatous polyposis requiring surgery. One of the long-term complications is pouch cancer, having a poor prognosis. The risk of high-grade dysplasia and cancer in the anal transitional zone and ileal pouch after 20 years is estimated to be 2 to 4.5% and 3 to 10% in ulcerative colitis and familial polyposis, respectively. The risk factors for ulcerative colitis are the presence of pre-operative dysplasia or cancer, disease duration > 10 years and severe villous atrophy. For familial polyposis, the risk factors are the number of pre-operative polyps > 1000, surgery with stapled anastomosis and the duration of follow-up. In the case of ulcerative colitis, a pouchoscopy should be performed annually if one of the following is present: dysplasia and cancer at surgery, primary sclerosing cholangitis, villous atrophy and active pouchitis (every 5 years without any of these factors). In the case of familial polyposis, endoscopy is recommended every year including chromoendoscopy. Even if anal transitional zone and ileal pouch cancers seldom occur following proctectomy for ulcerative colitis and familial adenomatous polyposis, the high mortality rate associated with this complication warrants endoscopic monitoring.

Факторы риска язвенного колита у детей

Актуальность. Воспалительные болезни кишечника на сегодняшний день являются одной из актуальных проблем детской гастроэнтерологии, что обусловлено стремительным распространением данной патологии, смещением дебюта болезни на ранний возраст ребенка (первые три года жизни), формированием тяжелых осложнений, низкой эффективностью современных схем лечения. Проблема язвенного колита у детей требует дальнейшего всестороннего изучения, в том числе факторов риска возникновения заболевания, что позволит формирование групп риска развития болезни, обоснование профилактических мероприятий по ее предупреждению. Материалы и методы. Изучение факторов риска проводилось путем опроса 100 матерей, дети которых болели язвенным колитом. Контрольную группу составили 30 матерей здоровых детей. Результаты. На основании математического анализа медико-биологических факторов риска развития язвенного колита у детей определены наиболее значимые: отягощенная наследственность по заболеваниям органов пищеварения, кишечные дисфункции в раннем возрасте, повторные курсы антибиотикотерапии, вторичная лактазная недостаточность, частые респираторные болезни. Разработан алгоритм прогнозирования язвенного колита в детском возрасте, обоснованы подходы к профилактике данной патологии.

Functional analysis of isoflavones using patient-derived human colonic organoids

Inflammatory bowel disease (IBD) comprises two major subtypes, ulcerative colitis (UC) and Crohn’s disease, which are multifactorial diseases that may develop due to genetic susceptibility, dysbiosis, or environmental factors. Environmental triggers of IBD include food-borne factors, and a previous nationwide survey in Japan identified pre-illness consumption of isoflavones as a risk factor for UC. However, the precise mechanisms involved in the detrimental effects of isoflavones on the intestinal mucosa remain unclear. The present study employed human colonic organoids (hCOs) to investigate the functional effect of two representative isoflavones, genistein and daidzein, on human colonic epithelial cells. The addition of genistein to organoid reformation assays significantly decreased the number and size of reformed hCOs compared with control and daidzein treatment, indicating an inhibitory effect of genistein on colonic cell/progenitor cell function. Evaluation of the phosphorylation status of 49 different receptor tyrosine kinases showed that genistein selectively inhibited phosphorylation of epidermal growth factor receptor (EGFR) and hepatocyte growth factor receptor (HGFR). We established a two-dimensional wound-repair model using hCOs and showed that genistein significantly delayed the overall wound-repair response. Our results collectively show that genistein may exert its detrimental effects on the intestinal mucosa via negative regulation of stem/progenitor cell function, possibly leading to sustained mucosal injury and the development of UC.

Evaluation of potential early life risk factors for ulcerative colitis

Amac: Erken yasam faktorlerinin bagirsak mikrobiyomunu etkileyerek iltihapli bagirsak hastaligi riskini etkileyebilecegi one surulmustur. Dogum sekli, anne sutu ve ebeveynlerin sigara icmesi en onemli cevresel faktorlerdir. Bu faktorlerin hastaligin yeri ve tani anindaki yas uzerindeki etkileri konusunda sinirli sayida calisma bulunmaktadir. Ayrica bu faktorlerin medikal tedavilere ve barsak tutulum yerine etkisi de bilinmemektedir. Yasamin ilk yillarinda yasanan potansiyel erken yasam risk faktorleri ile ulseratif kolit (UK) arasindaki iliskiyi inceledik. Yontemler: Bu calisma prospektif bir vaka kontrol calismasidir. Atmis dokuz UK hastasi yas ve cinsiyet bakimindan benzer 44 saglikli kontrol ile karsilastirildi. Potansiyel erken yasam risk faktoru olabilecek dogum sekli, anne sutu ile beslenme, anne dogum yasi, anne ve baba sigara kullanim durumlari arastirildi. UK hastalarinda bu potansiyel faktorlerin hastalik tani yasi, medikal tedavilerle iliskisi incelendi. Bulgular: UK ve kontrol grubu, dogum sekilleri, anne sutu ile beslenme, anne-baba sigara kullanma durumlari bakimindan karsilastirildiginda gruplar arasinda istatistiksel farklilik izlenmedi. Anne sutu alma sureleri bakimindan karsilastirildiginda ise 6-12 ay arasi anne sutu alanlar, UK grubunda daha dusuk saptanmistir (P=0,046). Ayrica anne sutu almayan UK hastalari ile annesi sigara kullanan UK hastalarinin hastalik tani yaslari daha dusuk bulunmustur (sirasiyla: P=0,031, P=0,016). Sonuclar: UK gelisimi acisindan emzirmenin suresi onemlidir. UK’den korunmak icin 6 aydan daha uzun anne sutu ile beslenme onermekteyiz. Erken baslangicli UK riski acisindan annenin sigarayi birakmasinin koruyucu rolu vardir.

P018 Per- and polyfluoroalkyl substances (PFAS) are significantly increased in patients with late-onset of ulcerative colitis

Abstract Background Environmental factors have been implicated in the pathogenesis of inflammatory bowel disease (IBD), particularly late onset disease. Per- and polyfluoroalkyl substances (PFAS) are man-made chemicals with a long biological half-life that have been extensively used since the 1950s and have been proposed to interfere with the bile acid synthesis. Therefore, to investigate if late onset IBD correlates with higher PFAS levels, we measured serum levels of PFAS and bile acids in patients diagnosed with IBD later in life. Methods Serum samples were collected from patients diagnosed with ulcerative colitis (n = 20) and Crohn’s disease (n = 20) at the age of ≥55 years. Blood donors (n = 20) were used as healthy controls and were matched by gender and age. The levels of PFAS and bile acids were assessed by ultra performance liquid chromatography coupled to a triple quadrupole mass spectrometer. Results The total amount of PFAS was significantly higher in patients with ulcerative colitis compared with healthy controls (p = 0.021) or patients with Crohn’s disease (p = 0.015). No difference was found in total PFAS levels between Crohn’s disease patients and healthy controls (p = 0.841). Seven out of 30 bile acids correlated to the total PFAS level. Conclusion Our results demonstrate that PFAS levels are increased in patients with late-onset of ulcerative colitis compared with Crohn’s disease patients and healthy controls. This finding indicates that PFAS might represent an environmental risk factor for ulcerative colitis. However, additional studies assessing the functional consequences of increased PFAS in late-onset ulcerative colitis are required to confirm this hypothesis.

The Role of Interleukin-22 Genetic Polymorphism in A Cohort of Egyptian Patients With Ulcerative Colitis

Background: Ulcerative colitis (UC) is characterized by an exaggerated mucosal immune response to luminal gut contents in genetically susceptible individuals. Interleukin-22 (IL-22) is a recently described IL-10 family cytokine that is produced by T-helper (Th)-17 cells, Th1 cells, NKT cells and newly described innate lymphoid cells (ILCs). Role for IL-22 has been identified in numerous tissues including the intestines, lung, liver, kidney, thymus, pancreas and skin. Aim of the work: studying the polymorphism of interleukin-22 in a cohort of Egyptian ulcerative colitis patients.Methods: The study included two groups Group A: fifty Egyptian patients suffering from ulcerative colitis. Group B: fifty Egyptian healthy persons as a control group. Genotypes of 3 common polymorphisms of the IL-22 gene were determined by the 5′ nuclease Allelic discrimination assay. Results: The comparison of IL22 rs2227485, rs1182844, and rs1179246 SNP genotype frequency between UC patients and controls revealed a statistically significant difference. Assessment of IL22 rs2227485, rs1182844, and rs1179246 SNPs as risk factors for UC using logistic regression analysis revealed that subject carrying one T, A and C alleles of the respective SNPs had 2.006, 2.676 and 4.416 folds increased risk for development of UC compared to the C, T and A alleles carriers respectively (OR=2.006, 95% C.I=1.044 – 3.854 for rs2227485 & OR=2.676, 95% C.I=1.394 – 5.135 for rs1182844 and OR=4.416, 95% C.I=2.372 – 8.221 for rs1179246).Conclusion: There was a significantly associated of IL-22 gene polymorphisms (rs2227485, rs1182844, rs1179246) with Egyptian UC patients. Additional well-designed large studies were required for the validation of our results.

Clinical features and risk factors of ulcerative colitis complicated with EB-viremia

Objective To analyze the clinical features and risk factors of ulcerative colitis (UC)complicated with Epstein-Barr(EB)-viremia and the effect of antiviral therapy on the remission of the symptoms. Methods From April 2014 to January 2018, data of 239 UC patients hospitalized at the Department of Gastroenterology of Second Hospital of Hebei Medical University were collected. The patients were divided into EB-viremia group (trial group, n=43) and non-EB-viremia group (control group, n=196) according to EB virus-DNA detection. The general condition, clinical characteristics and therapeutic efficacy of the two groups were compared. The risk factors and the effect of antiviral therapy on the remission of symptoms of UC complicated with EB-viremia were analyzed. Chi-square test and logistic analysis were used for statistical analysis. Results There were no significant differences in gender, age, clinical type, lesion range, the proportion of patients treated with 5-aminosalicylic acid or corticosteroids, the percentage of patients with diarrhea and bloody stool, the proportion of patients with spontaneous bleeding, platy ulcer and longitudinal ulcer under colonoscopy, the course of disease or Mayo score between the trial group and control group (all P>0.05). The proportions of patients with smoking history and severe disease, treatment with azathioprine and 6-mertocapurine (6-MP), treatrnent with infliximab, symptoms of fever or abdominal pain and deep and large ulcer under colonoscopy in the trial group were all higher than those in the control group, and the differences were all statistically significant (χ2=5.304, 6.608, 6.718, 6.939, 8.783, 4.493 and 5.425, all P 0.05). Conclusions Smoking history and purine treatment are risk factors of UC complicated with EB-viremia. Key words: Colitis, ulcerative; Risk factors; Epstein-Barr virus; Clinical manifestations; Endoscopic features

Is psychological stress a risk factor for ulcerative colitis?

Is psychological stress a risk factor for ulcerative colitis?

Late-Onset Crohn's Disease Is A Subgroup Distinct in Genetic and Behavioral Risk Factors With UC-Like Characteristics.

Age of onset is linked to variations in clinical phenotypes and natural history in Crohn's disease (CD). We aim to define etiologically more homogenous subgroups in CD based on ages of onset. We examined the distribution of CD polygenetic risk score (PRS) across ages of diagnosis in a Caucasian cohort of 2344 independent CD patients. We identified subgroups with a distinct distribution of PRS and compared those groups in genetics, demographic characteristics, clinical subphenotypes, and serological markers. The results were replicated in an independent cohort of 13,065 CD patients from the International Inflammatory Bowel Diseases Genetic Consortium (IIBDGC). We identified a late-onset (LO) subgroup in CD (age at diagnosis ≥ 55 years) with significantly lower PRS compared with the intermediate group (age at diagnosis between 5 and 55 years) in both cohorts. Smoking cessation, a risk factor for ulcerative colitis (UC) and protective factor for CD, had a higher rate in this LO subgroup in comparison with the intermediate group. We also compared the LO group with the intermediate group, and, consistent with previous reports, the LO group more often had colonic CD, had less penetrating disease behavior, and had less need for surgery. Serological analysis showed that LO CD patients were more antineutrophil cytoplasmic antibody positive and less antisaccharomyces cerevisiae antibody positive compared with the intermediate group. Variance component analysis indicated that overall genetic contribution to LO CD was lower relative to the middle group, and genetic heterogeneity testing indicated that LO CD was different from the middle group in underlying genetic architecture. Late-onset CD is subgroup distinct in genetic and behavioral risk factors with UC-like characteristics. 10.1093/ibd/izy148_video1izy148.video15791413461001.

Risk factors for inflammatory bowel disease: A prospective multi-center study.

Environmental risk factors have been associated with inflammatory bowel disease (IBD). With rising incidence, it is important to know risk factors associated with IBD in our population. This study was aimed to evaluate risk factors for IBD from western India. This was prospective, multi-center case-control study which included 1054 patients with IBD of which 765 (72.5%) were ulcerative colitis (UC) and 289 (27.4%) Crohn's disease (CD). Asymptomatic individuals without a history of any major illness served as controls. The questionnaire containing risk factors for IBD was given to patients and control group. Odds ratio and 95% confidence interval were calculated for each variable. Significant numbers of patients with CD were from rural area. Rural environment (OR 1.071, 0.82-1.38 and OR 1.441, 1.02-2.02), higher education (OR 1.830, 1.52-2.19 and OR 1.519, 1.16-1.97), professional by occupation (OR 1.754, 1.46-2.09 and OR 1.293, 0.99-1.67), annual family income >100,000 Indian national rupees (OR 2.185, 1.52-3.13 and OR 4.648, 3.10-6.95), history of appendectomy (OR 3.158, 1.71-5.80 and OR 3.158, 1.71-5.80), and family history of IBD (OR 4.510, 2.19-9.25 and OR 3.972, 1.58-9.96) were the risk factors for UC and CD, respectively. Vegetarian diet was protective factor for UC (OR 0.29, 0.27-0.39) and risk for CD (OR 1.179, 0.88-1.57). Smoking and chronic alcoholism were not found to be the risk factors. This study highlights association between socioeconomic, dietary factors, appendectomy, and family history as risk factors for IBD.

Childhood body mass index and risk of inflammatory bowel disease in adulthood: a population-based cohort study

The increasing incidence of inflammatory bowel disease (IBD) in western countries has led to the hypothesis that obesity-related inflammation could play a role in the etiology of IBD. However, this hypothesis lacks confirmation in studies of individuals prior to the typical onset of IBD in young adulthood. In a cohort of 316,799 individuals from the Copenhagen School Health Records Register (CSHRR), we examined whether BMI at ages 7 through 13 years was associated with later IBD. Linking the CSHRR to the Danish National Patient Register, we identified cases of Crohn's disease (CD) and ulcerative colitis (UC) diagnosed during follow-up. Cox regression was used to estimate the hazard ratios (HR) with 95% confidence intervals. During 10 million person-years of follow-up, 1500 individuals were diagnosed with CD and 2732 with UC. At all examined ages, a 1 unit increase in BMI z-score was associated with a significantly decreased risk of UC (HRs = 0.9) and with a significantly increased risk of CD when diagnosed before age 30 (HRs = 1.2). We observed no associations between changes in BMI z-score between 7 and 13 years and later risk of CD or UC. We found a direct association between childhood BMI and CD diagnosed before 30 years of age, and an inverse association between childhood BMI and UC irrespective of age. Our results support the previous hypotheses of obesity being a risk factor for CD, and suggest that childhood underweight might be a risk factor for UC.

Impact of Environmental and Familial Factors in a Cohort of Pediatric Patients With Inflammatory Bowel Disease.

The primary role of environment on inflammatory bowel disease (IBD) onset has been recently stressed. We aimed to investigate the effect of environmental factors in an IBD pediatric cohort. A total of 467 subjects (264 IBD and 203 controls) were enrolled. All patients underwent a questionnaire including 5 different groups of environmental risk factors: family history of IBD and autoimmune diseases, perinatal period, home amenities and domestic hygiene, childhood diseases and vaccinations, and diet. In a multivariate model, mother's degree (odds ratio [OR]: 5.5; 2.5-11.6), duration of breast feeding >3rd month (OR: 4.3; 1.6-10.5), father's employment (OR: 3.7; 1.2-8.7), gluten introduction <6th month (OR: 2.8; 1.5-5), number of siblings <2 (OR: 2.8; 1.5-5.3), and family history of autoimmune diseases (OR: 2.7; 1.4-5.3) were significant risk factors for Crohn disease. Low adherence to Mediterranean diet (OR: 2.3; 1.2-4.5), gluten introduction <6th month (OR: 2.8; 1.6-4.9), and number of siblings <2 (OR: 2; 1.1-3.6) were significant risk factors for ulcerative colitis. Owning pets (OR: 0.3; 0.1-0.7) and bed sharing (OR: 0.2; 0.1-0.6) were protective factors for Crohn disease, whereas owning pets (OR: 0.4; 0.2-0.8) and family parasitosis (OR: 0.07; 0.01-0.4) were protective factors for ulcerative colitis. Our study confirms that environmental factors are closely linked to IBD onset and may partly explain IBD rise in developed countries.

Epidemiology of inflammatory bowel disease among participants of the Millennium Cohort: incidence, deployment-related risk factors, and antecedent episodes of infectious gastroenteritis.

Crohn's disease (CD) and ulcerative colitis (UC) are two pathotypes of inflammatory bowel disease (IBD) with unique pathology, risk factors and significant morbidity. To estimate incidence and identify IBD risk factors in a US military population, a healthy subset of the US population, using information from the Millennium Cohort Study. Incident IBD was identified from medical encounters from 2001 to 2009 or by self-report. Our primary risk factor of interest, infectious gastroenteritis, was identified from medical encounters and self-reported post-deployment health assessments. Other potential risk factors were assessed using self-reported survey responses and military personnel files. Hazard ratios were estimated using Cox proportional hazards analysis. We estimated 23.2 and 21.9 diagnoses per 100 000 person-years, respectively, for CD and UC. For CD, significant risk factors included [adjusted hazard ratio (aHR), 95% confidence interval]: current smoking (aHR: 2.7, 1.4-5.1), two life stressors (aHR: 2.8, 1.4-5.6) and prior irritable bowel syndrome (aHR: 4.7, 1.5-15.2). There was no significant association with prior infectious gastroenteritis. There was an apparent dose-response relationship between UC risk and an increasing number of life stressors. In addition, antecedent infectious gastroenteritis was associated with almost a three-fold increase in UC risk (aHR: 2.9, 1.4-6.0). Moderate alcohol consumption (aHR: 0.4, 0.2-0.6) was associated with lower UC risk. Stressful conditions and the high risk of infectious gastroenteritis in deployment operations may play a role in the development of IBD in military populations. However, observed differences in risk factors for UC and CD warrant further investigation.

Inflammatory Potential of Diet and Risk of Ulcerative Colitis in a Case–Control Study from Iran

ABSTRACTDiet and inflammation have been suggested to be important risk factors for ulcerative colitis (UC). In this case–control study conducted in Iran, we examined the ability of the dietary inflammatory index (DII) to predict UC. This study included 62 UC cases and 124 controls hospitalized for acute non-neoplastic diseases. The DII was computed based on dietary intake assessed by a previously validated food frequency questionnaire. Multivariable logistic regression models were used to estimate odds ratios (ORs) and the DII was analyzed as both continuous and as tertiles. Energy was adjusted using the residual method. Subjects with higher DII scores (i.e., with a more pro-inflammatory diet) had a higher risk of UC, with the DII being used as both a continuous variable (ORcontinuous 1.55, 95% confidence interval (CI) 1.04–2.32; one unit increase corresponding to ≈8% of its range in the current study) and as tertiles (ORtertile3vstertile1 2.58, 95% CI 1.03–6.48, Ptrend| = |0.04). These results indicate that a pro-inflammatory diet is associated with increased risk of UC.

Interaction of MIF gene -173G/C polymorphism and GPX1 gene 594C/T polymorphism with high-fat diet in ulcerative colitis

To investigate the interaction of single nucleotide polymorphisms of macrophage migration inhibitory factor (MIF) gene -173G/C and glutathione peroxidase 1(GPX1) gene 594C/T polymorphisms and high-fat diet in ulcerative colitis (UC). The genetic polymorphisms of MIF -173G/C and GPX1 594C/T were determined with a polymorphism-polymerase chain reaction (PCR)-endonuclease method in peripheral blood leukocytes derived from 1500 UC cases and 1500 healthy controls. The frequencies of MIF -173CC and GPX1 594TT were 55.60% and 55.73% in the UC cases and 16.67% and 16.47% in the healthy controls, respectively. Statistical tests also showed a significant difference in the frequencies between the two groups (P<0.01; P<0.01, respectively). Individuals carrying MIF -173CC also had a significantly higher risk of UC compared with those with MIF -173GG (OR=6.8662, 95%CI: 4.5384-9.6158). Individuals carrying GPX1 594TT had a high risk of UC (OR=7.0854, 95%CI: 4.4702-10.5283). Combined analysis showed that the percentages of MIF -173CC/GPX1 594TT in the UC and control groups were 31.00% and 2.73%, respectively (P<0.01). Individuals carrying MIF -173CC/GPX1 594TT had a high risk of UC (OR=49.0113, 95%CI: 31.7364-61.8205). The high-fat diet rate of the case group was significantly higher than that of the control group (OR=3.3248, 95%CI: 1.9461-5.0193, P<0.01), and statistic analysis suggested an interaction between high-fat diet and MIF -173CC and GPX1 594TT which increase risk of UC (γ =6.9293; γ =6.9942). MIF -173CC and GPX1 594TT and high-fat diet are the risk factors for UC, and the significant interactions between genetic polymorphisms of MIF -173G/C, GPX1 594C/T and high-fat diet may increase the risk for UC.

Genetic polymorphisms of RAGE and risk of ulcerative colitis in a Chinese population

The receptor for advanced glycation end products (RAGE) and its proinflammatory ligands are critically implicated in the pathological progression of ulcerative colitis (UC). Functional polymorphisms in the regulatory elements and/or ligand-binding regions of the RAGE gene affect the expression and function of RAGE and thus may increase susceptibility to UC. In this study, a total of 266 unrelated UC patients and 247 control subjects were analyzed for 3 RAGE single nucleotide polymorphisms (SNPs) (−429 T/C, −374 T/A, and G82S) using an improved small-amplicon high resolution melting curve (HRM) analysis assay. Serum levels of soluble RAGE (sRAGE) were determined by a double sandwich ELISA system. The genotypes, alleles and haplotypes were analyzed and compared between UC patients and control subjects. Three pairs of genotyping primers for three RAGE polymorphism loci (−429 T/C, −374 T/A, and G82S) were developed based on HRM. Significant differences in the allele distribution of the G82S polymorphism was found among UC cases and controls from a Chinese population. Carriers of the RAGE G82S variant genotype were at higher risk of UC (OR=2.594, 95% CI: 1.778–3.784, P<0.001) than homozygous wild-type individuals. Further analyses revealed that the 82 (GS+SS) variant genotype was associated with patients who have extended UC (OR=1.924, 95% CI: 1.163–3.181, P=0.010), and a family history of inflammatory bowel disease (IBD) (OR=1.923, 95% CI: 1.049–3.521, P=0.032). The polymorphisms −374 T/A and −429 T/C did not demonstrate any association with UC, but an association was found between the −374(TA+AA) variant genotypes and the serum sRAGE level (P=0.002). Moreover, haplotypes T/A/A and T/A/G showed significantly different frequencies between UC patients and controls (OR=3.337, 95% CI: 1.892–6.091, P=0.026; OR=0.530, 95% CI: 0.351–0.801, P=0.002). The present study developed novel primers based on HRM to provide preliminary evidence in a Chinese population that the RAGE polymorphism is involved in genetic susceptibility to UC and that the 82(GS+SS) genotype of G82S is a risk factor for UC. Furthermore, RAGE polymorphisms may be related to the location of UC as well as a family history of IBD in a Chinese population.

Interaction between the polymorphisms of cyclooxygenase-2-1195G/A,MnSOD9Ala/val genes and the high-fat diets and its correlation with ulcerative colitis.

To investigate the interaction of the polymorphisms of cyclooxygenase-2-1195G/A (COX-2-1195G/A) and manganese superoxide dismutase 9Ala/Val (MnSOD9Ala/Val) genes and the high-fat diets and its potential correlation with ulcerative colitis (UC). The genetic polymorphisms of COX-2-1195G/A and MnSOD9Ala/Val were analyzed by polymorphism-polymerase chain reaction (PCR) in peripheral blood leukocytes obtained from 750 UC patients (UC group) and 750 healthy subjects (control group). The frequencies of COX-2-1195G/A(A/A) and MnSOD9Ala/Val(V/V) were 49.07% and 50.13% in UC group and 21.20% and 22.40% in control group, respectively (P<0.01). The risk of UC significantly increased in subjects with COX-2-1195G/A(A/A) genotype (OR=3.5808,95%CI=1.8062-5.3478) and in those with MnSOD9Ala/Val(V/V) genotype(OR=3.4828,95%CI=1.9137-5.5496). Pooled analysis of the polymorphisms showed that distribution frequency of COX-2-1195G/A(A/A)/MnSOD9Ala/Val (V/V) was 40.67% in UC group and 8.40% in control group (P<0.01). Subjects with COX-2-1195G/A(A/A)/MnSOD9Ala/Val(V/V) had a significantly higher risk of UC (OR=7.5655,95% CI=4.1849-11.2037). The rate of high-fat diets was significantly higher in the UC group than in the control group(49.73 vs.20.13%,P<0.01),and statistic analysis suggested an interaction between high-fat diet and COX-2-1195G/A(A/A)(Γ=11.81821)and MnSOD9Ala/Val (V/V)(Γ=9.0107), which increase risk of UC. COX-2-1195G/A(A/A),MnSOD9Ala/Val (V/V), and high-fat diet are the risk factors of UC. The interaction between the genetic polymorphisms of COX-2-1195G/A and MnSOD9Ala/Val and the high-fat diet increases the risk of UC.