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ELife Feb 2023Whether the positive associations of smoking and alcohol consumption with gastrointestinal diseases are causal is uncertain. We conducted this Mendelian randomization...
BACKGROUND
Whether the positive associations of smoking and alcohol consumption with gastrointestinal diseases are causal is uncertain. We conducted this Mendelian randomization (MR) to comprehensively examine associations of smoking and alcohol consumption with common gastrointestinal diseases.
METHODS
Genetic variants associated with smoking initiation and alcohol consumption at the genome-wide significance level were selected as instrumental variables. Genetic associations with 24 gastrointestinal diseases were obtained from the UK Biobank, FinnGen study, and other large consortia. Univariable and multivariable MR analyses were conducted to estimate the overall and independent MR associations after mutual adjustment for genetic liability to smoking and alcohol consumption.
RESULTS
Genetic predisposition to smoking initiation was associated with increased risk of 20 of 24 gastrointestinal diseases, including 7 upper gastrointestinal diseases (gastroesophageal reflux, esophageal cancer, gastric ulcer, duodenal ulcer, acute gastritis, chronic gastritis, and gastric cancer), 4 lower gastrointestinal diseases (irritable bowel syndrome, diverticular disease, Crohn's disease, and ulcerative colitis), 8 hepatobiliary and pancreatic diseases (non-alcoholic fatty liver disease, alcoholic liver disease, cirrhosis, liver cancer, cholecystitis, cholelithiasis, and acute and chronic pancreatitis), and acute appendicitis. Fifteen out of 20 associations persisted after adjusting for genetically predicted alcohol consumption. Genetically predicted higher alcohol consumption was associated with increased risk of duodenal ulcer, alcoholic liver disease, cirrhosis, and chronic pancreatitis; however, the association for duodenal ulcer did not remain statistically significant after adjustment for genetic predisposition to smoking initiation.
CONCLUSIONS
This study provides MR evidence supporting causal associations of smoking with a broad range of gastrointestinal diseases, whereas alcohol consumption was associated with only a few gastrointestinal diseases.
FUNDING
The Natural Science Fund for Distinguished Young Scholars of Zhejiang Province; National Natural Science Foundation of China; Key Project of Research and Development Plan of Hunan Province; the Swedish Heart Lung Foundation; the Swedish Research Council; the Swedish Cancer Society.
Topics: Humans; Mendelian Randomization Analysis; Genetic Predisposition to Disease; Duodenal Ulcer; Smoking; Alcohol Drinking; Esophageal Neoplasms; Liver Diseases, Alcoholic; Gastritis; Pancreatitis, Chronic; Genome-Wide Association Study; Polymorphism, Single Nucleotide
PubMed: 36727839
DOI: 10.7554/eLife.84051 -
World Journal of Gastroenterology Oct 2019() is a gram-negative bacterium that infects approximately 4.4 billion individuals worldwide. However, its prevalence varies among different geographic areas, and is... (Review)
Review
() is a gram-negative bacterium that infects approximately 4.4 billion individuals worldwide. However, its prevalence varies among different geographic areas, and is influenced by several factors. The infection can be acquired by means of oral-oral or fecal-oral transmission, and the pathogen possesses various mechanisms that improve its capacity of mobility, adherence and manipulation of the gastric microenvironment, making possible the colonization of an organ with a highly acidic lumen. In addition, presents a large variety of virulence factors that improve its pathogenicity, of which we highlight cytotoxin associated antigen A, vacuolating cytotoxin, duodenal ulcer promoting gene A protein, outer inflammatory protein and gamma-glutamyl transpeptidase. The host immune system, mainly by means of a Th1-polarized response, also plays a crucial role in the infection course. Although most -positive individuals remain asymptomatic, the infection predisposes the development of various clinical conditions as peptic ulcers, gastric adenocarcinomas and mucosa-associated lymphoid tissue lymphomas. Invasive and non-invasive diagnostic methods, each of them with their related advantages and limitations, have been applied in detection. Moreover, bacterial resistance to antimicrobial therapy is a major challenge in the treatment of this infection, and new therapy alternatives are being tested to improve eradication. Last but not least, the development of effective vaccines against infection have been the aim of several research studies.
Topics: Antacids; Anti-Bacterial Agents; Bacterial Vaccines; Drug Resistance, Bacterial; Drug Therapy, Combination; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Probiotics; Proton Pump Inhibitors; Stomach Diseases; Treatment Outcome; Virulence Factors
PubMed: 31602159
DOI: 10.3748/wjg.v25.i37.5578 -
Nature Communications Feb 2021Genetic factors are recognized to contribute to peptic ulcer disease (PUD) and other gastrointestinal diseases, such as gastro-oesophageal reflux disease (GORD),...
Genetic factors are recognized to contribute to peptic ulcer disease (PUD) and other gastrointestinal diseases, such as gastro-oesophageal reflux disease (GORD), irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). Here, genome-wide association study (GWAS) analyses based on 456,327 UK Biobank (UKB) individuals identify 8 independent and significant loci for PUD at, or near, genes MUC1, MUC6, FUT2, PSCA, ABO, CDX2, GAST and CCKBR. There are previously established roles in susceptibility to Helicobacter pylori infection, response to counteract infection-related damage, gastric acid secretion or gastrointestinal motility for these genes. Only two associations have been previously reported for duodenal ulcer, here replicated trans-ancestrally. The results highlight the role of host genetic susceptibility to infection. Post-GWAS analyses for PUD, GORD, IBS and IBD add insights into relationships between these gastrointestinal diseases and their relationships with depression, a commonly comorbid disorder.
Topics: ABO Blood-Group System; Antigens, Neoplasm; CDX2 Transcription Factor; Depression; Duodenal Ulcer; Female; Fucosyltransferases; GPI-Linked Proteins; Galactosyltransferases; Gastroesophageal Reflux; Gastrointestinal Diseases; Genetic Predisposition to Disease; Genome-Wide Association Study; Helicobacter Infections; Helicobacter pylori; Humans; Inflammatory Bowel Diseases; Male; Mucin-1; Mucin-6; Neoplasm Proteins; Peptic Ulcer; Galactoside 2-alpha-L-fucosyltransferase
PubMed: 33608531
DOI: 10.1038/s41467-021-21280-7 -
Translational Psychiatry May 2023The causality of the association between depression and gastrointestinal diseases is undetermined. We conducted Mendelian randomization (MR) analyses to systematically...
The causality of the association between depression and gastrointestinal diseases is undetermined. We conducted Mendelian randomization (MR) analyses to systematically explore the associations of depression with 24 gastrointestinal diseases. Independent genetic variants associated with depression at the genome-wide significance level were selected as instrumental variables. Genetic associations with 24 gastrointestinal diseases were obtained from the UK Biobank study, the FinnGen study, and large consortia. Multivariable MR analysis was conducted to explore the mediation effects of body mass index, cigarette smoking, and type 2 diabetes. After multiple-testing corrections, genetic liability to depression was associated with an increased risk of irritable bowel syndrome, non-alcohol fatty liver disease, alcoholic liver disease, gastroesophageal reflux, chronic pancreatitis, duodenal ulcer, chronic gastritis, gastric ulcer, diverticular disease, cholelithiasis, acute pancreatitis, and ulcerative colitis. For the causal effect of genetic liability to depression on non-alcoholic fatty liver disease, a substantial proportion was mediated by body mass index. Genetic predisposition to smoking initiation mediated half of effect of depression on acute pancreatitis. This MR study suggests that depression may play a causal role in many gastrointestinal diseases.
Topics: Humans; Pancreatitis; Acute Disease; Depression; Diabetes Mellitus, Type 2; Mendelian Randomization Analysis; Gastrointestinal Diseases; Genome-Wide Association Study; Polymorphism, Single Nucleotide
PubMed: 37142593
DOI: 10.1038/s41398-023-02459-6 -
JPMA. the Journal of the Pakistan... Jul 2023Duodenal ulcer perforation, a frequent surgical emergency, needs simple closure with indirect Graham's Omentopexy which is effective with excellent results in majority...
Duodenal ulcer perforation, a frequent surgical emergency, needs simple closure with indirect Graham's Omentopexy which is effective with excellent results in majority of cases despite patients' late presentation. The objective of the study was to determine the frequency of postoperative complications of perforated duodenal ulcer, conducted in the Surgery Department, Jinnah Postgraduate Medical Centre, Karachi, from March 20, 2018 to September 20, 2018. The study was a descriptive case series of 108 patients of both genders with perforated duodenal ulcer > 1 week old with ASA score I & II. Patients with trauma and comorbidities were excluded. The patients underwent laparotomy and peritoneal toilet, and after noting the site of perforation indirect Graham's Omentopexy was performed. Complications like duodenal fistula, peritonitis, and paralytic ileus, and patient's death within 10 days of surgery were noted. Age ranged from 18 to 50 years with mean age of 35.027±5.13 years, mean weight 71.120±12.77 kg, mean height 1.541 ±0.09 metres, mean BMI 29.975±4.99 kg/m2, and the mean duration of complaint was 4.194±1.30 weeks. Male predominance in 75 (69.4%) patients. Duodenal fistula was seen in 10 (9.3%) patients, peritonitis 12 (11.1%), paralytic ileus 14 (13%) and mortality was in 11 (10.2%) patients.
Topics: Humans; Male; Female; Adult; Infant; Duodenal Ulcer; Risk Factors; Peptic Ulcer Perforation; Peritonitis; Fistula
PubMed: 37469068
DOI: 10.47391/JPMA.4768