Repeat polymorphisms in the Homo sapiens heme oxygenase-1 gene in diabetic and idiopathic gastroparesis.

BACKGROUND: Idiopathic and diabetic gastroparesis in Homo sapiens cause significant morbidity. Etiology or risk factors have not been clearly identified. Failure to sustain elevated heme oxygenase-1 (HO1) expression is associated with delayed gastric emptying in diabetic mice and polymorphisms in the HO1 gene (HMOX1, NCBI Gene ID:3162) are associated with worse outcomes in other diseases. AIM: Our hypothesis was that longer polyGT alleles are more common in the HMOX1 genes of individuals with gastroparesis than in controls without upper gastrointestinal motility disorders. METHODS: Repeat length was determined in genomic DNA. Controls with diabetes (84 type 1, 84 type 2) and without diabetes (n = 170) were compared to diabetic gastroparetics (99 type 1, 72 type 2) and idiopathic gastroparetics (n = 234). Correlations of repeat lengths with clinical symptom sub-scores on the gastroparesis cardinal symptom index (GCSI) were done. Statistical analyses of short (<29), medium and long (>32) repeat alleles and differences in allele length were used to test for associations with gastroparesis. RESULTS: The distribution of allele lengths was different between groups (P = 0.016). Allele lengths were longest in type 2 diabetics with gastroparesis (29.18±0.35, mean ± SEM) and longer in gastroparetics compared to non-diabetic controls (28.50±0.14 vs 27.64±0.20 GT repeats/allele, P = 0.0008). Type 2 diabetic controls had longer alleles than non-diabetic controls. In all gastroparetic groups, allele lengths were longer in African Americans compared to other racial groups, differences in the proportion of African Americans in the groups accounted for the differences between gastroparetics and controls. Diabetic gastroparetics with 1 or 2 long alleles had worse GCSI nausea sub-scores (3.30±0.23) as compared to those with 0 long alleles (2.66±0.12), P = 0.022. CONCLUSIONS: Longer poly-GT repeats in the HMOX1 gene are more common in African Americans with gastroparesis. Nausea symptoms are worse in subjects with longer alleles.

Prevalence, Risk Factors, and Outcomes of Irritable Bowel Syndrome After Infectious Enteritis: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: Foodborne illness affects 15% of the US population each year, and is a risk factor for irritable bowel syndrome (IBS). We evaluated risk of, risk factors for, and outcomes of IBS after infectious enteritis. METHODS: We performed a systematic review of electronic databases from 1994 through August 31, 2015 to identify cohort studies of the prevalence of IBS 3 months or more after infectious enteritis. We used random-effects meta-analysis to calculate the summary point prevalence of IBS after infectious enteritis, as well as relative risk (compared with individuals without infectious enteritis) and host- and enteritis-related risk factors. RESULTS: We identified 45 studies, comprising 21,421 individuals with enteritis, followed for 3 months to 10 years for development of IBS. The pooled prevalence of IBS at 12 months after infectious enteritis was 10.1% (95% confidence interval [CI], 7.2-14.1) and at more than 12 months after infectious enteritis was 14.5% (95% CI, 7.7-25.5). Risk of IBS was 4.2-fold higher in patients who had infectious enteritis in the past 12 months than in those who had not (95% CI, 3.1-5.7); risk of IBS was 2.3-fold higher in individuals who had infectious enteritis more than 12 months ago than in individuals who had not (95% CI, 1.8-3.0). Of patients with enteritis caused by protozoa or parasites, 41.9% developed IBS, and of patients with enteritis caused by bacterial infection, 13.8% developed IBS. Risk of IBS was significantly increased in women (odds ratio [OR], 2.2; 95% CI, 1.6-3.1) and individuals with antibiotic exposure (OR, 1.7; 95% CI, 1.2-2.4), anxiety (OR, 2; 95% CI, 1.3-2.9), depression (OR, 1.5; 95% CI, 1.2-1.9), somatization (OR, 4.1; 95% CI, 2.7-6.0), neuroticism (OR, 3.3; 95% CI, 1.6-6.5), and clinical indicators of enteritis severity. There was a considerable level of heterogeneity among studies. CONCLUSIONS: In a systematic review and meta-analysis, we found >10% of patients with infectious enteritis develop IBS later; risk of IBS was 4-fold higher than in individuals who did not have infectious enteritis, although there was heterogeneity among studies analyzed. Women-particularly those with severe enteritis-are at increased risk for developing IBS, as are individuals with psychological distress and users of antibiotics during the enteritis.

New and Investigational Agents for Irritable Bowel Syndrome.

Irritable bowel syndrome (IBS) affects about 15 % of the US population and results in significant morbidity and health care costs. There remains a significant unmet need for effective treatments particularly for the pain component of IBS and other functional gastrointestinal disorders (FGIDs). Progress made in our understanding of pathophysiological mechanisms such as the role of altered bile acid metabolism, neurohormonal regulation, immune dysfunction, the epithelial barrier and secretory properties of the gut has led to advancements in therapeutic armamentarium for IBS. This review discusses the new drugs for constipation and diarrhea-predominant IBS subtypes that have been tested or have been under investigation over the last 3-4 years. Overall, there is a promising pipeline of investigational drugs for the future treatment of IBS and related FGIDs.