Search

Background: African Americans (AAs) are an admixed population of West African (WA) and European ancestry (EA). Crohn's disease (CD) susceptibility genes have not been established. We therefore evaluated the contribution of European admixture and major established risk genes to AA CD., Methods: Ninety-seven admixture informative markers were genotyped for ancestry estimates using STRUCTURE. Overall, 354 AA CD cases and 354 ethnicity-matched controls were genotyped for total 21 single nucleotide polymorphisms (SNPs) in ATG16L1, NOD2, IBD5, IL23R and IRGM by TaqMan or direct sequencing. Association was evaluated by logistic regression, adjusted for ancestry., Results: Mean EA was similar among the CD cases and controls (20.9% and 20.4%, respectively, P = 0.58). No significant admixture differences were observed among 211 to 227 cases stratified by phenotypic subclassifications including onset, surgery, site, and behavior. CD was associated with NOD2 carrier (6.93% CD, 2.15% Controls, P = 0.007), ATG16L1 Thr300Ala (36.1% CD, 29.3% Controls, P = 0.003), SLC22A4 and SLC22A5 (IBD5 locus) functional SNPs (Leu503Phe [10.5% CD, 7.6% Controls, P = 0.05] and g-207c [41.3% CD, 35.7% Controls, P = 0.03], respectively), and IL23R rs2201841 (18.2% CD, 13.8% Controls, P = 0.03), but not IRGM variants, nor three African ancestral NOD2 nonsynonymous variants. IBD5 risk was recessive. An all-minor allele IBD5 haplotype from EA was associated (P = 0.05), whereas a more common haplotype isolating g-207c was not., Conclusions: Specific functional gene variations contribute significantly to AA CD risk. Established NOD2, SLC22A4-A5, and ATG16L1 variants show increased CD risk, with IBD5 recessive. Although CD is more common in whites, European admixture is similar among AA cases and controls., (Copyright © 2012 Crohn's & Colitis Foundation of America, Inc.)

Background: Crohn's disease (CD) and ulcerative colitis (UC) are associated with expression differences in genes involved in immune function, wound healing, and tissue remodeling. MicroRNAs (miRNAs) are small, noncoding RNAs that act as potent negative regulators of gene expression and are differentially expressed in chronic inflammatory diseases, including UC. We examined the expression of miRNAs in tissues from different intestinal regions and in patients with active ileal and colonic CD., Methods: Colonoscopic pinch biopsies were obtained from the terminal ileum, cecum, transverse colon, sigmoid colon, and rectum of normal, healthy adults and from the ileum and sigmoid colon of patients with active ileal and colonic CD. miRNA expression was assessed using miRNA microarray and validated by mature miRNA quantitative reverse-transcription polymerase chain reaction (RT-PCR)., Results: Ten intestine region-specific miRNAs were identified. Three miRNAs were increased and one miRNA was decreased in the terminal ileum as compared to the colon. Six other miRNAs expressed varying levels of expression among the colon regions. Five miRNAs were found to be differentially expressed in tissues of patients with active colonic CD, with three increased and two decreased as compared to normal, healthy controls. Similarly, four miRNAs were found to be significantly increased in tissues of patients with active ileal CD., Conclusions: The expression differences between ileal CD, colonic CD, and previously identified UC-associated miRNAs support the likelihood that miRNAs influence differing inflammation-related gene expression in each inflammatory bowel disease (IBD) subtype and may form the basis for future diagnostic tests and therapeutic targets for IBD.

Background: Adherence plays an important role in the therapeutic effectiveness of medical therapy in inflammatory bowel disease (IBD). We assessed whether trust-in-physician and Black race were predictors of adherence., Methods: We performed a cross-sectional study of Black (n = 120) and White (n = 115) IBD patients recruited from an outpatient IBD clinic. Self-reported adherence to taking medication and keeping appointments, trust-in-physician, and health-related quality of life were measured using the validated instruments, the modified Hill-Bone Compliance Scale (HBCS), the Trust-in-Physician Scale (TIPS), and the Short IBD Questionnaire (SIBDQ), respectively., Results: Overall adherence was 65%. Higher adherence correlated with greater trust-in-physician (r = -0.30; P < 0.0001), increasing age (r = -0.19; P = 0.01), and worsening health-related quality of life (r = -0.18; P = 0.01). Adherence was also higher among White IBD patients compared to Blacks (HBSC: 15.6 versus 14.0, P < 0.0001). Trust-in-physician, race, and age remained predictors of adherence to medical management after adjustment for employment, income, health insurance, marital and socioeconomic status, and immunomodulator therapy. The adjusted odds ratio for adherence in Blacks compared to Whites was 0.29 (95% confidence interval: 0.13-0.64). Every half standard deviation increase in trust-in-physician and every incremental decade in age were associated with 36% and 47% higher likelihood of adherence, respectively., Conclusions: Trust-in-physician is a potentially modifiable predictor of adherence to IBD medical therapy. Black IBD patients exhibited lower adherence compared to their White counterparts. Understanding the mechanisms of these racial differences may lead to better optimization of therapeutic effectiveness.

Background: One of the most common symptoms among patients with inflammatory bowel disease (IBD) is diarrhea, which is thought to be contributed by changes in electrolyte transport associated with intestinal inflammation. This study was designed to test the hypothesis that intestinal Na(+)-related transporters/channels and their regulatory proteins may be downregulated as a potential contributor to IBD-associated diarrhea., Methods: SDS-PAGE and Western blotting and/or confocal immunomicroscopy were used to examine the expression of Na(+)/H(+)-exchangers 1-3 (NHE1-3), epithelial Na(+) channel (ENaC), Na(+)/K(+)-ATPase, the intracellular Cl(-) channel 5 (ClC-5), and NHE3 regulatory factors (NHERF1,2) in ileal and colonic pinch biopsies from IBD patients and noninflammatory controls, as well as from colonic mucosa of dextran sodium sulfate (DSS)- and TNBS-induced acute murine IBD models., Results: NHE1,3 (but not NHE2), beta-ENaC, Na(+)/K(+)-ATPase-alpha, ClC-5, and NHERF1 were all downregulated in sigmoid mucosal biopsies from most cases of active UC and/or CD compared to controls. NHE3 was also decreased in ileal mucosal biopsies of active CD, as well as in approximately 50% of sigmoid biopsies from inactive UC or CD. Importantly, similar downregulation of NHE1,3, beta-ENaC, and NHERF1,2 was also observed in the mouse colon (but not ileum) of DSS- and TNBS-induced colitis., Conclusions: IBD-associated diarrhea may be due to a coordinated downregulation of multiple Na(+) transporter and related regulatory proteins, including NHE1,3, Na(+)/K(+)-ATPase, and ENaC, as well as NHERF1,2, and ClC-5, all of which are involved directly or indirectly in intestinal Na(+) absorption.

Background: Inflammatory bowel disease (IBD) patients are at increased risk of protein-calorie malnutrition. We sought to determine the prevalence of clinically diagnosable malnutrition among those hospitalized for IBD throughout the United States and whether this malnutrition influenced health outcomes., Methods: We queried the Nationwide Inpatient Sample between 1998 and 2004 to identify admissions for Crohn's disease (CD) or ulcerative colitis (UC) and a representative sample of non-IBD discharges. We assessed the prevalence and predictors of malnutrition and its association with in-hospital mortality and resource utilization., Results: The prevalence of malnutrition was greater in CD and UC patients than in non-IBD patients (6.1% and 7.2% versus 1.8%, P < 0.0001). The adjusted odds ratio for malnutrition among IBD admissions compared with non-IBD admissions was 5.57 [95% confidence interval (CI): 5.29-5.86]. More IBD discharges than non-IBD discharges with malnutrition received parenteral nutrition (26% versus 6%, P < 0.0001). There was increased likelihood of malnutrition among those with fistulizing CD (OR 1.65; 95% CI: 1.50-1.82) and among those who had undergone bowel resection (OR 1.37; 95% CI: 1.27-1.48). Malnutrition was associated with increased in-hospital mortality 3.49 (95% CI: 2.89-4.23), length of stay (11.9 days versus 5.8 days, P < 0.00001), and total charges ($45,188 versus $20,295, P < 0.0001)., Conclusions: Clinically apparent malnutrition is more frequent among IBD admissions than among non-IBD admissions. Its association with greater mortality and resource utilization may reflect more severe underlying disease that can lead to both malnutrition and worse outcomes. Nonetheless, diagnosable malnutrition may serve as a clinical marker of poor IBD prognosis in hospitalized patients.

Background: Recent epidemiological studies suggest that the prevalences of Crohn's disease (CD) and ulcerative colitis (UC) are increasing in the United States. We sought to determine whether nationwide rates of inflammatory bowel disease (IBD) hospitalizations have increased in response to temporal trends in prevalence., Methods: We identified all admissions with a primary diagnosis of CD or UC, or 1 of their complications in the Nationwide Inpatient Sample between 1998 and 2004. National estimates of hospitalization rates and rates of surgery were determined using the U.S. Census population as the denominator., Results: There were an estimated 359,124 and 214,498 admissions for CD and UC, respectively. The overall hospitalization rate for CD was 18.0 per 100,000 and that for UC was 10.8 per 100,000. There was a 4.3% annual relative increase in hospitalization rate for CD (P < 0.0001) and a 3.0% annual increase for UC (P < 0.0001). Surgery rates were 3.4 bowel resections per 100,000 for CD and 1.2 colectomies per 100,000 for UC and remained stable. There were no temporal patterns for average length of stay for CD (5.8 days) or for UC (6.8 days). The national estimate of total inpatient charges attributable to CD increased from $762 million to $1,330 million between 1998 and 2004, and that for UC increased from $592 million to $945 million., Conclusions: Hospitalization rates for IBD, particularly CD, have increased within a 7-year period, incurring a substantial rise in inflation-adjusted economic burden. The findings reinforce the need for effective treatment strategies to reduce IBD complications.

Background: Ulcerative colitis (UC) and Crohn's disease (CD) are inflammatory bowel diseases (IBD) with variable, overlapping clinical features and complex pathophysiologies., Methods: To identify pathogenic processes underlying these disease subtypes, we used single endoscopic pinch biopsies to elucidate patterns of gene expression in active and inactive areas of UC and CD and compared these to infectious colitis and healthy control samples., Results: Unsupervised classification of a total of 36 samples yielded promising separation between the affected IBD, unaffected IBD, non-IBD colitis, and normal control samples, suggesting each sample type had a distinctive gene expression pattern. Genes differentially expressed in the CD samples compared to in the controls were related to IFNgamma-inducible TH1 processes (IFITM1, IFITM3, STAT1, and STAT3) and antigen presentation (TAP1, PSME2, PSMB8). The most noticeable change in the UC samples was reduced expression of genes regulating biosynthesis, metabolism, and electrolyte transport (HNF4G, KLF5, AQP8, ATP2B1, and SLC16A). Twenty-five percent of genes down-regulated in the UC samples were also down-regulated in the infectious colitis samples. Unaffected biopsy samples of IBD patients also registered differences expression of genes compared to in the normal controls. Of these differentially expressed genes, only 2 were up-regulated, PSKH1, a regulator of mRNA processing, and PPID, a suppressor of apoptosis., Conclusions: The study shows that the gene expression patterns of IBD, CD in particular, are quite different from those of infectious colitis, highlighting distinctive expression of genes and pathways in UC and CD.