Caucasian Inflammatory Bowel Disease Research Articles

Urinary manifestations in African American and Caucasian inflammatory bowel disease patients: a retrospective cohort study

BackgroundInflammatory bowel diseases (IBD), like ulcerative colitis (UC) and Crohn’s disease (CD), are associated with urinary extra-intestinal manifestations, like urolithiasis and uncomplicated urinary tract infections (UTIs). The literature reviewed for this study identifies an increased association of CD and urolithiasis against the general population as well as UC. Furthermore, the rates in which urinary comorbidities manifest have not been well characterized in cross-race analyses. The purpose of this study is to establish the prevalence of common urinary extra-intestinal manifestations in CD and UC and to further determine at what rate these affect the African American and Caucasian populations.MethodologyThis is a retrospective cohort study using de-identified data collected from a research data base that included 6 integrated facilities associated with one tertiary healthcare center from 2012 to 2019. The electronic chart records for 3104 Caucasian and African American IBD patients were reviewed for frequency of urolithiasis and uncomplicated UTI via diagnosed ICD-10 codes. Comparison between data groups was made using multivariate regressions, t-tests, and chi square tests.ResultsOur study included 3104 patients of which 59% were female, 38% were African American, and 43% were diagnosed with UC. Similar proportions of UC and CD diagnosed patients developed urolithiasis (6.0% vs 6.7%, p = 0.46), as well as uncomplicated UTIs (15.6% vs. 14.9%, p = 0.56). Similar proportions of African American and Caucasian patients developed urolithiasis (5.4% vs 7.0%, p = 0.09), but a higher proportion of African Americans developed uncomplicated UTIs (19.4% vs 12.6%, p ≤ 0.001).ConclusionWe found similar rates of urolithiasis formation in both UC and CD in this study. Furthermore, these rates were not significantly different between African American and Caucasian IBD populations. This suggests that UC patients have an elevated risk of urolithiasis formation as those patients with CD. Additionally, African Americans with IBD have a higher frequency of uncomplicated UTI as compared to their Caucasian counterparts.

The dietary practices and beliefs of British South Asian people living with inflammatory bowel disease: a multicenter study from the United Kingdom

Background/AimsEpidemiological associations have implicated factors associated with Westernization, including the Western diet, in the development of inflammatory bowel disease (IBD). The role of diet in IBD etiopathogenesis, disease control and symptom management remains incompletely understood. Few studies have collected data on the dietary habits of immigrant populations living with IBD. Our aim was to describe the dietary practices and beliefs of British South Asians with IBD.MethodsA 30-item questionnaire was developed and consecutively administered to 255 British South Asians with IBD attending gastroenterology clinics in the United Kingdom.ResultsFifty-one percent of participants believed diet was the initiating factor for their IBD and 63% felt diet had previously triggered disease relapse. Eighty-nine percent avoided certain dietary items in the belief that this would prevent relapse. The most commonly avoided foods and drinks were spicy and fatty foods, carbonated drinks, milk products, alcohol, coffee, and red meat. A third of patients had tried a whole food exclusion diet, most commonly lactose- or gluten-free, and this was most frequently reported amongst those with clinically active IBD (P = 0.02). Almost 60% of participants avoided eating the same menu as their family, or eating out, at least sometimes, to prevent IBD relapse.ConclusionsBritish South Asians with IBD demonstrate significant dietary beliefs and food avoidance behaviors with increased frequency compared to those reported in Caucasian IBD populations. Studies in immigrant populations may offer valuable insights into the interaction between diet, Westernization and cultural drift in IBD pathogenesis and symptomatology.

Associations between Gene Polymorphisms in Pro-inflammatory Cytokines and the Risk of Inflammatory Bowel Disease: A Meta-analysis

ABSTRACT The relationships between polymorphisms in pro-inflammatory cytokines and the risk of inflammatory bowel disease (IBD) remain discrepant. Therefore, the authors conducted a meta-analysis to robustly explore relationships between polymorphisms in pro-inflammatory cytokines and the risk of IBD by integrating the results of previous works. Medline, Embase, Wanfang, VIP and CNKI were searched throughly for eligible studies, and 35 genetic association studies were finally included in this meta-analysis. We noticed that genotypic frequencies of IL-1B rs1143627, IL-6 rs1800795 and IL-8 rs4073 polymorphisms among cases with IBD and population-based controls differed significantly. Moreover, we found that genotypic frequencies of IL-1B rs1143627 and IL-6 rs1800795 polymorphisms among cases with IBD and population-based controls of Caucasian origin differed significantly, whereas genotypic frequency of IL-8 rs4073 and IL-18 rs187238 polymorphisms among cases with IBD and population-based controls of Asian origin also differed significantly. Furthermore, we also noticed that genotypic frequency of IL-18 rs187238 polymorphism among cases with Crohn’s disease (CD) and population-based controls differed significantly. In conclusion, this meta-analysis demonstrated that IL-1B rs1143627 and IL-6 rs1800795 polymorphisms were significantly associated with the risk of IBD in overall population and Caucasians. Moreover, IL-8 rs4073 polymorphism was significantly associated with the risk of IBD in overall population and Asians. In addition, we also noticed that IL-18 rs187238 polymorphism was significantly associated with the risk of CD, and IL-18 rs1946518 polymorphism was significantly associated with the risk of IBD in Asians.

Comparison of Emergency Room Use Between African-American and Caucasian Inflammatory Bowel Disease (IBD) Patients

Aim: Inflammatory bowel disease (IBD) is a chronic condition becoming increasingly prevalent in the African-American (AA) population. We aimed to compare ED utilization between AA and non-Hispanic Caucasian (C) IBD patients in a large tertiary care referral center. Material and Methods: A retrospective chart view was performed on IBD patients seen in the Emory University Hospital ED after Institutional Review Board approval. Results: Data from 391 patients including 244 C patients and 147 AA patients was available for analysis. There were more AA patients who had ≥ 2 ED visits compared to C patients. When assessing the number of ED visits based on whether the visits were IBD-related vs non-IBD related, more AA patients had ≥ 2 visits for both types of visits. In the multivariable logistic regression analysis, factors associated with IBD related visits included younger age, AA race, male sex, a diagnosis of ulcerative colitis, being a current patient in the Emory GI clinic, and prior history of IBD-related surgery. Conclusion: Our study reveals that AA IBD patients seen in the ED more individuals visited the ED more than once for both IBD and non-IBD related issues compared to C IBD patients.

HIGH PREVALENCE OF UNTREATED AND UNDERTREATED VITAMIN D DEFICIENCY AND INSUFFICIENCY IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE.

SUMMARYInflammatory bowel disease (IBD) patients with vitamin D deficiency show an increased risk of hospital admission, surgery, and loss of response to biologic therapy while high vitamin D levels are identified as a protective factor. Our goal was to investigate the prevalence of untreated and undertreated vitamin D deficiency and factors associated with vitamin D deficiency. In this cross-sectional study, we measured serum vitamin D in a random sample of Caucasian IBD patients. Vitamin D deficiency was defined as <50 nmol/L and insufficiency as 50-75 nmol/L. Supplementation was defined as taking 800-2000 IU vitamin D daily. Untreated patients were defined as not taking supplementation and undertreated group as receiving supplementation but showing vitamin D deficiency or insufficiency despite treatment. Our study included 185 IBD patients, i.e. 126 (68.1%) with Crohn’s disease (CD) and 59 (31.9%) with ulcerative colitis (UC). Overall, 108 (58.4%) patients had vitamin D deficiency and 60 (32.4%) patients vitamin D insufficiency. There were 16 (14.8%) and 11 (18.3%) treated patients in vitamin D deficiency and vitamin D insufficiency group, respectively. The rate of untreated patients was 81.7% (n=49) in vitamin D deficiency group and 85.2% (n=92) in vitamin D insufficiency group. Tumor necrosis factor alpha inhibitors were associated with higher serum vitamin D levels in CD and UC, and ileal involvement, ileal and ileocolonic resection with lower levels. In conclusion, not only is vitamin D deficiency common in IBD patients but the proportion of untreated and undertreated patients is considerably high. We suggest regular monitoring of vitamin D levels in IBD patients regardless of receiving vitamin D supplementation therapy.

810 Disparities in Objective Sleep Quality as Assessed by Wrist Actigraphy in Minority Patients With Inflammatory Bowel Disease

INTRODUCTION: Inflammatory Bowel Disease (IBD) is associated with a reduced quality of life, including a high incidence of poor sleep. Minority patients with IBD describe poorer subjective symptoms of disease. Minority patients are more likely to report poorer sleep quality compared to Caucasian patients. There are limited data on the assessment of sleep in minority patients with IBD. In this prospective cohort study, we aim to compare objective sleep parameters assessed by wrist actigraphy in minority IBD patients compared to Caucasian IBD patients. METHODS: 73 patients with a diagnosis of IBD were recruited to take part in this IRB approved study. Subjects were stratified into two cohorts by self-identification: minority subjects (Blacks and Non-Black Hispanic subjects) and Caucasian, non-minority individuals. Subjects were excluded based on significant co-morbidity, a history of a sleep disorder, or demographics which did not fit into categorized cohorts. Subjects completed sleep surveys and were provided with an accelerometer that estimated sleep patterns. Comparisons of actigraphic parameters were performed between minority and non-minority cohorts. Regression analyses were performed to determine whether minority status was independently associated with poorer sleep parameters assessed by actigraphy. Predictors that were found to be different by &lt; 0.1 between cohorts were included in the models. RESULTS: Of the recruited subjects, 64 subjects completed 3 days of actigraphy data. 33 subjects were minority patients and 31 individuals were non-minority patients. The demographics of the cohorts are provided in Table 1. Table 2 details the univariate analyses. A higher proportion of minority patients had poorer sleep efficiency (SE) and fragmented sleep compared to Caucasian patients (90.9% vs. 67.7%, P = 0.03 and 87.8% vs. 61.3%, P = 0.02). Minority status was independently associated with both poor SE (OR: 6.41 CI: 1.48-28.17, P = 0.0139) and fragmented sleep (OR: 4.98, CI: 1.09-22.89, P = 0.0389), (Tables 3.0A and 3.0B). CONCLUSION: In our study minority subjects were found to have poorer objective measures of sleep assessed by actigraphy compared to non-minority subjects. Culturally relevant care addressing psychosocial issues, including sleep are important in the care of minority patients with IBD. Further studies investigating the role of sleep in diverse populations with IBD are warranted to determine the etiologies of poor sleep in these patients.

Correlations between TLR polymorphisms and inflammatory bowel disease: a meta-analysis of 49 case-control studies.

Recently, the roles of toll-like receptor (TLR) polymorphisms in inflammatory bowel disease (IBD) were intensively explored, with conflicting results. Therefore, we performed this study to better assess the relationship between TLR polymorphisms and the risk of IBD. Eligible studies were searched in PubMed, Medline, Embase, and Web of Science. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to estimate associations between TLR polymorphisms and IBD. Significant associations with the risk of IBD were detected for the TLR1 rs5743611, TLR4 rs4986790, TLR4 rs4986791, and TLR6 rs5743810 polymorphisms in overall analyses. Further subgroup analyses according to ethnicity of participants revealed that the TLR1 rs5743611, TLR4 rs4986790, TLR4 rs4986791, TLR6 rs5743810, and TLR9 rs352140 polymorphisms were significantly associated with the risk of IBD in Caucasians. Moreover, the TLR4 rs4986790 polymorphism was significantly correlated with the risk of IBD in West Asians, while the TLR9 rs352140 polymorphism was significantly associated with the risk of IBD in Africans. When we stratified available data according to type of disease, we found similar positive results for TLR1 rs5743611, TLR4 rs4986790, TLR4 rs4986791, and TLR6 rs5743810 polymorphisms. Our findings indicate that TLR1 rs5743611, TLR4 rs4986790, TLR4 rs4986791, TLR6 rs5743810, and TLR9 rs352140 polymorphisms may serve as genetic biomarkers of IBD in certain ethnicities. However, further well-designed studies are still warranted to confirm our findings.

African American Ethnicity Associated with Decreased Odds of Inflammatory Bowel Disease: Results of a Nationwide Analysis

Introduction: Inflammatory bowel disease (IBD) affects all ethnicities worldwide, with the highest prevalence in North America and Europe. While several studies have suggested a higher occurrence of IBD in Caucasians, most prior studies were performed on Caucasian-predominant populations. The aim of this study was to assess the occurrence of IBD in African American (AA) patients in the US. Methods: This was a case-control study using the National Inpatient Sample 2014, a US inpatient database. All patients with ICD-9 CM codes corresponding to IBD were included. There were no exclusion criteria. AA were identified within the database from the ethnic categories. Population estimates were obtained from the U.S. National Census Bureau. The primary outcome was the occurrence and odds of IBD in the AA population compared to other ethnicities. Secondary outcomes were inpatient mortality, morbidity, as measured by shock, ICU stay, multi-organ failure and colectomy; resource utilization, including use of abdominal CT and colonoscopy; length of hospital stay, hospitalization charges and costs. Propensity score matching was used to create a 1:1 matching population, and was regressed against gender, age and Charlson Comorbidity Index. Multivariate regression analyses were used to adjust for income in patients' zip code, hospital region, location, size and teaching status. Results: 32,665 cases of IBD were identified in the AA population and propensity-matched. The mean patient age was 44 years, 58% were female. The prevalence of IBD in admitted AA was 80/100,000 persons (330/100,000 admissions), compared to 100/100,000 persons (1,147/100,000 admissions) of other ethnicities. Adjusting for confounders, admitted AA patients displayed adjusted matched odds of 0.60 (p<0.01) of having IBD compared to other admitted ethnicities. All outcomes are in Table 1. For secondary outcomes, AA displayed higher propensity-matched odds of CT abdomen (aOR:2.20, p<0.01) and multi-organ failure (aOR:1.24, p<0.01), but lower odds of TPN (aOR:0.80, p=0.02). All ethnicities did not differ in odds of mortality, shock, ICU stay or abdominal ultrasound. Conclusion: The national prevalence of IBD is lower in the AA population, which corroborates findings of prior smaller studies. Although, the odds of AA patients having IBD are markedly decreased compared to other ethnicities, AA displayed higher odds of CT abdomen, colonoscopy and multi-organ failure, potentially reflecting a worse disease course.729 Figure 1. - Adjusted means and odds ratios for evaluated parameters in African Americans compared to other ethnicities with inflammatory bowel disease.

Characteristics of Anemia and Inflammatory Bowel Disease (IBD) Activity in African American versus Caucasian Patients: An Experience at an Urban Tertiary Referral IBD Center From 2008-2018

Introduction: Anemia is a common extra-intestinal complication of inflammatory bowel disease (IBD). Epidemiologic studies of United States IBD patients are limited. Our study compares the features of anemia as well as disease activity in African American (AA) and Caucasian IBD patients at an urban tertiary referral IBD center.2805 Figure 1. Patient demographics, disease characteristics, anemia features, and healthcare utilization statistics (a) definition of anemia: men with Hb <13 g/dL, in nonpregnant women <12 g/dL, in pregnant women <11 g/dL. (b) Mild anemia (Hb 11-13 g/dL in male and 11-12 g/dL in female), moderate anemia (Hb 8-11 g/dL in both sex) and severe anemia (Hb <8 g/dL in both sex).Methods: Inpatient and outpatient charts of IBD patients presenting from 2008-2018 to an inner-city tertiary referral center were reviewed for: clinical data, labs, endoscopy, imaging, surgery and IBD medication use. WHO criteria defined severity of anemia. Iron deficiency was defined as a ferritin Results: A total of 278 patients were included in the analysis. Sixty patients (21.5%) were African American, 183 patients (66%) were Caucasian, and 35 patients (12.5%) were neither. Anemia characteristics, IBD demographics, and disease activity were compared between AA and Caucasian population. (Table 1) AA population had a greater proportion of anemic patients compared to Caucasian population during the follow up duration (63% vs 48%, p 0.04). However, there was no statistical difference in iron supplementation between the two groups (38% vs 30%, p 0.2). AA patients were noted to have more active disease compared to Caucasian patients during the time of their lowest hemoglobin level. (Active disease on endoscopy or imaging 70% vs 55%, p 0.04 and higher ESR value 22.5 vs 13 mm/hr, p 0.004). AAs were likely to require more all-cause hospital admissions compared to Caucasian patients (63% vs 48%, p 0.04). There was no significant difference in usage of biologics or immunomodulators. Conclusion: In our study, AA patients demonstrated more active disease as well as higher prevalence of anemia subsequently requiring more hospital admissions compared to the Caucasian population. However, there was no difference in IBD as well as anemia management between these two groups. Underlying etiology of these findings requires further research but our study emphasizes the need for closer monitoring and treatment of AA patients with IBD.

Nonsynonymous Polymorphism in Guanine Monophosphate Synthetase Is a Risk Factor for Unfavorable Thiopurine Metabolite Ratios in Patients With Inflammatory Bowel Disease.

Up to 20% of patients with inflammatory bowel disease (IBD) who are refractory to thiopurine therapy preferentially produce 6-methylmercaptopurine (6-MMP) at the expense of 6-thioguanine nucleotides (6-TGN), resulting in a high 6-MMP:6-TGN ratio (>20). The objective of this study was to evaluate whether genetic variability in guanine monophosphate synthetase (GMPS) contributes to preferential 6-MMP metabolizer phenotype. Exome sequencing was performed in a cohort of IBD patients with 6-MMP:6-TGN ratios of >100 to identify nonsynonymous single nucleotide polymorphisms (nsSNPs). In vitro assays were performed to measure GMPS activity associated with these nsSNPs. Frequency of the nsSNPs was measured in a cohort of 530 Caucasian IBD patients. Two nsSNPs in GMPS (rs747629729, rs61750370) were detected in 11 patients with very high 6-MMP:6-TGN ratios. The 2 nsSNPs were predicted to be damaging by in silico analysis. In vitro assays demonstrated that both nsSNPs resulted in a significant reduction in GMPS activity (P < 0.05). The SNP rs61750370 was significantly associated with 6-MMP:6-TGN ratios ≥100 (odds ratio, 5.64; 95% confidence interval, 1.01-25.12; P < 0.031) in a subset of 264 Caucasian IBD patients. The GMPS SNP rs61750370 may be a reliable risk factor for extreme 6MMP preferential metabolism.

Association between KIR-HLA combination and ulcerative colitis and Crohn's disease in a Japanese population.

Inflammatory bowel disease (IBD) consists of ulcerative colitis (UC) and Crohn’s disease (CD). Natural killer cell responses play a crucial role in autoimmune disease through innate immunity, in which killer cell immunoglobulin-like receptors (KIRs) are closely involved. Although the genetic combination of KIRs with their specific HLA class I ligands has been associated with IBD in Caucasians, such KIR-HLA receptor-ligand combinations are not fully understood in the Japanese. We investigated 14 KIR genes along with HLA-Bw and -C ligands in 90 patients with UC and 50 patients with CD and compared them with the characteristics of 325 healthy control subjects. The frequency of HLA-Bw4 was significantly increased in patients with UC (P = 1.3 × 10−6; odds ratio [OR] = 3.39) and CD (P = 0.0065; OR = 2.32) versus controls. The UC group had a significantly higher frequency of KIR2DS3 (P = 0.024; OR = 1.94) and lower frequency of KIR2DS4 (P = 0.019; OR = 0.40) and KIR2DL1-HLA-C2 (P = 0.035; OR = 0.47). The Tel-A/B haplotype was significantly decreased in UC patients (P = 0.0056; OR = 0.49). The frequency of KIR3DL1-HLA-Bw4 was significantly higher in patients with UC (P = 4.3 × 10−6; OR = 3.12) and CD (P = 0.0067; OR = 2.30). In conclusion, HLA-Bw4 and KIR-HLA pairs may play an important role in the genetic susceptibility to IBD in the Japanese.

Impact of Race on Loss of Response to Infusion Biologics in Inflammatory Bowel Disease Patients in a Tertiary Care Referral Center

Introduction: Inflammatory bowel disease (IBD) is a chronic condition becoming increasingly prevalent in the African-American (AA) population. There is limited data on treatment outcomes between the two populations. We aimed to compare treatment outcomes and disparities in Caucasian (C) and AA patients receiving infliximab and vedolizumab. Methods: A retrospective chart view was performed on IBD patients newly started on infliximab and vedolizumab at Emory University between 2012-2016 after IRB approval. Clinical and demographic variables were analyzed. Continuous variable were compared using student t test, and categorical variables were compared using Chi square test. Binary logistic regression modeling was utilized to determine likelihood predictors of loss of response (LOR). Results: A total of 150 patients were selected including 95 C and 47 AA patients. Table 1 highlights the demographic and clinical comparisons of the groups. A trend towards CD C patients being older than AA (p=0.08) was found as well as more thiopurine use at induction (p=0.07) in C CD patients. Body mass index (BMI) did not differ between the two groups. However, in UC patients, a trend towards more AA patients being obese than C patients pre and post 1-year treatment (p=0.057) was identified. No differences in LOR, time to LOR, or changes in management following LOR was seen between AA and Caucasians patients with IBD. On binary logistic regression race, gender, and age were not predictive of LOR for all comers, p=0.53. In our CD cohort, there was a trend towards LOR to infliximab (OR 4.69, p=0.07) and vedolizumab (OR 0.21, p=0.07) in AA compared to Caucasians when the logistic regression was adjusted for age and gender.Table: Clinical and demographic characteristics by race. Please see the JPEG file for Table 1.Conclusion: Our study reveals similarities and subtle differences in outcomes of AA and Caucasian IBD patients treated with vedolizumab and infliximab. While it is known that AA patients are 1.5x more likely to be obese compared to C patients, our CD cohort did not show a difference between the two populations in terms of percent obesity. However, there was a trend towards more AA UC patients to be obese than C patients, similar to the general population. While race was not a predictor for LOR for all comers, within the CD cohort, we did find a trend towards LOR to infliximab and vedolizumab in AA compared to C, which may be due to findings of possible less thiopurine use in AA CD patients. Such subtle disparities warrant further study in larger cohorts.

Pregnane X Receptor Polymorphisms and Risk of Inflammatory Bowel Disease: A Meta-Analysis

ABSTRACTBackground: Pregnane X receptor (PXR) gene polymorphisms have been widely studied in terms of the association with inflammatory bowel disease (IBD), with inconsistent results.Objective: The present meta-analysis was performed to assess the association between PXR gene polymorphisms and the susceptibility of IBD, Crohn’s disease (CD), and ulcerative colitis (UC).Methods: PubMed, Wanfang, and CNKI databases were searched for eligible studies before November 1, 2016. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to calculate the various genetic models using either a fixed-effect or a random-effect model. The heterogeneity of the included studies was examined with Cochran Q and I2 statistics. Begg’s rank correlation test and Egger’s linear regression test were used to assess the publication bias.Results: A total of six studies with 4248 cases and 3853 controls were included in this meta-analysis. Three PXR gene polymorphisms were evaluated: rs1523127, rs2276707, and rs6785049. Our analyses of rs1523127, rs2276707, and rs6785049 suggested that PXR gene polymorphism had no obvious influence on the risk of IBD in Caucasians. Subgroup analyses based on disease type showed similar results.Conclusion: Our meta-analysis revealed that PXR gene polymorphism may not be significantly associated with IBD susceptibility. However, the number of original studies was limited and further studies with large samples are needed to verify the results.Abbreviations: PXR = pregnane X receptor, IBD = inflammatory bowel disease, CD = Crohn’s disease, UC = ulcerative colitis, ORs = pooled odds ratios, 95% CIs = 95% confidence intervals, NOS = Newcastle–Ottawa scale, HWE = Hardy–Weinberg equilibrium.

Su1007 - A Comparison of Hospitalizations of African-American and Caucasian Inflammatory Bowel Disease (IBD) Patients in A Tertiary Care Referral Center

Su1007 - A Comparison of Hospitalizations of African-American and Caucasian Inflammatory Bowel Disease (IBD) Patients in A Tertiary Care Referral Center

Glutathione S-Transferase T1 Null Genotype is Associated with Susceptibility to Inflammatory Bowel Disease

Background: The published literature contains conflicting results regarding the impact of the glutathione S-transferase T1 (GSTT1) null genotype on the susceptibility to inflammatory bowel disease. Therefore, we conducted a meta-analysis of observational studies to assess the association. Methods: We searched four online databases for eligible studies. The odds ratio (OR) with 95% CI was used to assess the gene-disease association. We also performed subgroup analyses by type of inflammatory bowel disease and ethnicity. Results: There were 16 individual studies from 11 publications included in the analysis. There were 3366 cases with inflammatory bowel disease and 6013 controls. The meta-analysis of all 16 studies showed the GSTT1 null genotype was associated with increased susceptibility to inflammatory bowel disease (OR = 1.98, 95%CI 1.39-2.84, P < 0.001). The subgroup analysis by ethnicity further identified an association between the GSTT1 null genotype and inflammatory bowel disease in Caucasians, Asians, and Africans. The GSTT1 null genotype was associated with both ulcerative colitis (OR = 1.96, P = 0.004) and Crohn’s disease (OR = 2.01, P = 0.022). The GSTT1 null genotype was still significantly associated with ulcerative colitis (OR = 1.63, P < 0.0001) and Crohn’s disease (OR = 1.40, P = 0.023) after adjusting for study heterogeneity. Conclusion: The GSTT1 null genotype is significantly associated with an increased susceptibility to inflammatory bowel disease and is a risk factor for both ulcerative colitis and Crohn’s disease.

Relationship between IL-10 gene -819C/T polymorphism and the risk of inflammatory bowel disease: a meta-analysis.

The -819C/T polymorphism in interleukin 10 (IL-10) gene has been reported to be associated with inflammatory bowel disease (IBD), but the previous results are conflicting. The present study aimed at investigating the association between this polymorphism and risk of IBD using a meta-analysis.PubMed, Web of Science,EMBASE,google scholar and China National Knowledge Infrastructure (CNKI) databases were systematically searched to identify relevant publications from their inception to April 2016.Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using fixed- or random-effects models. A total of 7 case-control studies containing 1890 patients and 2929 controls were enrolled into this meta-analysis, and our results showed no association between IL-10 gene -819C/T polymorphism and IBD risk(TT vs. CC:OR=0.81,95%CI 0.64-1.04;CT vs. CC:OR=0.92,95%CI 0.81-1.05; Dominant model: OR=0.90,95%CI 0.80-1.02; Recessive model: OR=0.84,95%CI 0.66-1.06). In a subgroup analysis by nationality, the -819C/T polymorphism was not associated with IBD in both Asians and Caucasians. In the subgroup analysis stratified by IBD type, significant association was found in Crohn's disease(CD)(CT vs. CC:OR=0.68,95%CI 0.48-0.97). In summary, the present meta-analysis suggests that the IL-10 gene -819C/T polymorphism may be associated with CD risk.

Covering the Cover

Covering the Cover

Characterization of Genetic Loci That Affect Susceptibility to Inflammatory Bowel Diseases in African Americans

Inflammatory bowel disease (IBD) has familial aggregation in African Americans (AAs), but little is known about the molecular genetic susceptibility. Mapping studies using the Immunochip genotyping array expand the number of susceptibility loci for IBD in Caucasians to 163, but the contribution of the 163 loci and European admixture to IBD risk in AAs is unclear. We performed a genetic mapping study using the Immunochip to determine whether IBD susceptibility loci in Caucasians also affect risk in AAs and identify new associated loci. We recruited AAs with IBD and without IBD (controls) from 34 IBD centers in the United States; additional controls were collected from 4 other Immunochip studies. Association and admixture loci were mapped for 1088 patients with Crohn's disease, 361 with ulcerative colitis, 62 with IBD type unknown, and 1797 controls; 130,241 autosomal single-nucleotide polymorphisms (SNPs) were analyzed. The strongest associations were observed between ulcerative colitis and HLA rs9271366 (P= 7.5 × 10(-6)), Crohn's disease and 5p13.1 rs4286721 (P= 3.5 × 10(-6)), and IBD and KAT2A rs730086 (P= 2.3 × 10(-6)). Additional suggestive associations (P < 4.2 × 10(-5)) were observed between Crohn's disease and IBD and African-specific SNPs in STAT5A and STAT3; between IBD and SNPs in IL23R, IL12B, and C2orf43; and between ulcerative colitis and SNPs near HDAC11 and near LINC00994. The latter 3 loci have not been previously associated with IBD, but require replication. Established Caucasian associations were replicated in AAs (P < 3.1 × 10(-4)) at NOD2, IL23R, 5p15.3, and IKZF3. Significant admixture (P < 3.9 × 10(-4)) was observed for 17q12-17q21.31 (IZKF3 through STAT3), 10q11.23-10q21.2, 15q22.2-15q23, and 16p12.2-16p12.1. Network analyses showed significant enrichment (false discovery rate <1 × 10(-5)) in genes that encode members of the JAK-STAT, cytokine, and chemokine signaling pathways, as well those involved in pathogenesis of measles. In a genetic analysis of 3308 AA IBD cases and controls, we found that many variants associated with IBD in Caucasians also showed association evidence with these diseases in AAs; we also found evidence for variants and loci not previously associated with IBD. The complex genetic factors that determine risk for or protection against IBD in different populations require further study.

Susceptibility to IBD is associated with with specific KIR and HLA ligand genotypes (BA4P.142)

Abstract Adaptive and innate host immune responses to intestinal microbes have been implicated in the pathogenesis of Ulcerative Colitis and Crohn’s Disease, the subtypes of Inflammatory Bowel Disease (IBD). Polymorphisms of the Killer Ig-like Receptors (KIR) genes, which encode receptors on natural killer cells, influence immune mediated diseases. Here we study the genetic contribution of KIR and their HLA ligands in UC and CD. HLA genotyping was performed by next generation sequencing and KIR genotyping with our MALDI-TOF assay. The KIR HLA ligands, Bw4/6 and C1/C2 were assigned using HLA-B and HLA-C residue positions 77-83. The case-control analysis consisted of 1232 Caucasian IBD patients (461 with UC, 771 with CD) and 203 Caucasian controls. The homozygous genotypic combination of KIR2DL3, KIR3DL1 (homozygous KIR A/A haplotype) and Bw6 (absence of Bw4) with a heterozygous C1/C2 genotype was protective (cf, C1/C1 and C2/C2) against ulcerative colitis (OR = 0.29, p &amp;lt; 0.001). No significant association was found with KIR loci and their HLA-ligands with CD. In a C1/C2 heterozygote, signaling would be expected via both the KIR2DL3 receptor and the KIR2DL1 receptor. These data reveal a central role for a specific combination of KIRs and HLA ligands (i.e., homozygous KIR A haplotype, absence of Bw4 and C1/C2 heterozygosity) in protecting against UC disease and underscore the importance of analyzing KIR genotypes in the context of their HLA ligands in disease association studies.

Tu1242 Factors Associated With the Use of Corticosteroid-Sparing Medications Among Elderly Veterans With Inflammatory Bowel Disease

Background: High quality care in inflammatory bowel disease (IBD) includes complex medical therapies that require adherence to treatment plans and frequent monitoring. Studies of IBD patients in the United States have identified race-based differences in healthcare delivery and utilization. Prior investigations of race and medication adherence in IBD have relied on survey tools and self-reporting. Our aim was to compare medication adherence between African American (AA) and Caucasian (C) IBD patients using objective pharmacy refill data. Methods: After Emory IRB approval, we retrospectively reviewed the charts of IBD patients treated in a tertiary center's subspecialty IBD clinic between 10/2013 and 12/ 2013. Medication adherence was determined using electronic pharmacy refill data (including all pharmacies used by the patient) for the 6 months following a visit to the IBD clinic. Poor adherence was defined as a medication possession ratio of <0.8 during the periods that the patient was prescribed the medication. Data was collected on rates of disease flares over this 6-month period. Statistical analysis included Mann-Whitney U for continuous variables and Chi-square testing for categorical variables, as well as a logistic regression analysis. Results: One hundred and sixty IBD patient charts were reviewed (53% F, mean age 44.1 ± 1.3). In this cohort, 23% were AA, 69.4% C, and 6.6% other races (33% UC, 65% CD, and 2% indeterminate colitis). Twenty-five percent were new patients and 75% established patients. Among AA patients, 81.1% were adherent to medications (n=30/37), as compared to 88.3% of C patients (n=98/111). This differencewas not statistically significant (p=0.3). No difference was seen in anti-TNF therapy prescriptions, where 33.3% of C patients and 43.2% of AA were prescribed biologics (p=0.2). Patients who were non-adherent to medical therapy were more likely to be younger than adherent patients (age 33 vs.46, p= 0.001). In a logistic regression model adjusting for sex, race, prior surgery, and prior hospital admission, younger age was the only significant predictor of poor adherence to IBD therapies (OR= 0.9, 95% CI 0.9-0.98, p<0.01). Non-adherent patients had more flares (0.8 vs.0.4 flares/patient in 6 months, p=0.014), and were prescribed a larger number of IBDmedications (1.6 vs.1 medication, p<0.01). Conclusions: An objective evaluation of medication refills in AA and C IBD patients seen in the same clinic revealed no significant differences in medication adherence. The only significant predictor of poor adherence was younger age. Lower medication adherence was associated with increased IBD flares, as well as being prescribed a larger number of IBD medications. While prospective validation is needed, this suggests that race-based disparities in medication adherence are decreased with similar access to care.