Colonic Diverticulosis. Is there a Genetic Component?
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ABSTRACT:
SUBMITTER: Ana Maria Miulescu M
PROVIDER: S-EPMC7221275 | biostudies-literature | 2020 Mar
REPOSITORIES: biostudies-literature
Publications
Diverticular disease is a common condition among the elderly, with a steady increase in prevalence over time. Also, it has a temporal, geographic, and ethnic variation in incidence and prevalence, the genetic component having only recently been studied. For many years, environmental factors were the main link to the etiology. Recent studies estimated the heritability in this disease and identified genetic variants associated with diverticulosis. The interaction between structural changes of the ...[more]
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Project description:BackgroundThe prevalence of diverticulosis has increased in our aging population, but the risk factors for diverticulosis are not fully understood. The role of hypertension in the risk of diverticulosis remains uncertain. This study investigated whether hypertension is associated with asymptomatic colorectal diverticulosis.MethodsThis study enrolled asymptomatic patients who received a colonoscopy as part of a health check. Hypertension was defined by actual measured blood pressure. Logistic regression models were used to examine the relationship between hypertension and diverticulosis. In addition, we established three logistic regression models for covariate adjustment, and further stratified patients with hypertension into three subgroups based on their type of hypertension.ResultsThe study group consisted of 2748 participants, including 141 participants with diverticulosis and 2607 participants without diverticulosis. After adjustments for potential covariates, the odds ratio (OR) for having diverticulosis was 1.83 (95% confidence interval, 1.21-2.75, p = 0.004) in the hypertension group compared with the group without hypertension. In subgroup analyses, hypertension without antihypertensive medication use, and hypertension despite the use of antihypertensive medication were also significantly associated with the occurrence of asymptomatic diverticulosis (OR = 1.73, p = 0.028; OR = 2.07, p = 0.013, respectively). Current normal blood pressure under antihypertensive drug therapy was not associated with diverticulosis (OR = 1.74, p = 0.092).ConclusionsOur findings suggest a positive association between hypertension and diverticulosis. Participants with poorly controlled blood pressure were found to have a higher risk of asymptomatic diverticulosis. Our study presents epidemiologic evidence for future prevention strategies against diverticulosis.
| S-EPMC6580716 | biostudies-literature
Project description:Background & aimsObesity has been associated with an increased risk of colonic diverticulosis. Evidence for this association is limited. We assessed whether anthropometric measures of obesity were associated with colonic diverticulosis.MethodsWe analyzed data from a prospective study of 623 patients undergoing screening colonoscopies from 2013 through 2015; colonoscopies included examinations for diverticulosis. Body measurements were made the day of the procedure. Multivariate analyses were performed using modified Poisson regression to estimate prevalence ratios (PRs) and 95% CIs while adjusting for confounding variables. All analyses were stratified by sex.ResultsAmong men, there was no association between any measure of obesity and diverticulosis. After adjustment, women with an obese body mass index (BMI ? 30) had an increased risk of any diverticulosis (PR, 1.48; 95% CI, 1.08-2.04) compared with women with a normal body mass index (BMI 18.5-24.9). The strength of this association was greater for more than 5 diverticula (PR, 2.05; 95% CI, 1.23-3.40). There was no significant association between measures of central obesity and diverticulosis in women. Stratified by sex, colonic diverticulosis was significantly less prevalent in women compared with men before the age of 51 years (29% vs 45%, P = .06). The prevalence of diverticulosis did not differ by sex in older age groups.ConclusionsIn an analysis of data from 623 patients undergoing screening colonoscopies, we found that obesity (BMI ?30) significantly increased the risk of colonic diverticulosis in women but not men. Colonic diverticulosis was less prevalent in premenopausal-age women compared with similar-age men. These findings suggest that sex hormones may influence the development of diverticulosis.
| S-EPMC6842072 | biostudies-literature
Project description:Diverticulosis results from the development of pouch-like structures, called diverticula, over the colon. The etiology of the disease is poorly understood resulting in a lack of effective treatment approaches. It is well known that mechanical stress plays a major role in tissue remodeling, yet its role in diverticulosis has not been studied. Here, we used computational mechanics to investigate changes in stress distribution engendered over the colon tissue by the presence of a pouch-like structure. The objectives of the study were twofold: (1) observe how stress distribution changes around a single pouch and (2) evaluate how stress elevation correlates with the size of the pouch. Results showed that high stresses are concentrated around the neck of a pouch, and their values and propagation increase with the size of the pouch neck rather than the pouch surface area. These findings suggest that stress distribution may change in diverticulosis and a vicious cycle may occur where pouch size increases due to stress elevation, which in turn elevates stress further and so on. Significant luminal pressure reduction would be necessary to maintain stress at normal level according to our results and therapeutic approaches aimed directly at reducing stress should rather be sought after.
| S-EPMC7138845 | biostudies-literature
Project description:BACKGROUND/OBJECTIVES:The possible relationship between smoking and risk of colonic diverticulosis has been suggested by recent epidemiological studies, although the results were inconsistent. This meta-analysis was conducted to summarize all available data. METHODS:A comprehensive literature review was conducted using the MEDLINE and EMBASE databases through May 2017 to identify all studies that compared the risk of colonic diverticulosis among current and former smokers versus nonsmokers. Effect estimates from each study were extracted and combined together using the random-effect, generic inverse variance method of DerSimonian and Laird. RESULTS:Of 465 potentially eligible articles, three prospective cohort studies with 130,520 participants met the eligibility criteria and were included in the meta-analysis. The risk of colonic diverticulosis in current smokers was significantly higher than nonsmokers with the pooled risks ratio of 1.46 (95% confidence interval [CI], 1.13-1.89). However, the risk of colonic diverticulosis in former smokers was not significantly higher than nonsmokers with the pooled risk ratio of 1.13 (95% CI, 0.88-1.44). CONCLUSIONS:A significantly increased risk of colonic diverticulosis among current smokers is demonstrated in this study.
| S-EPMC5820812 | biostudies-literature
Project description:The statements produced by the Consensus Conference on Diverticular Disease promoted by GRIMAD (Gruppo Italiano Malattia Diverticolare, Italian Group on Diverticular Diseases) are reported. Topics such as epidemiology, risk factors, diagnosis, medical and surgical treatment of diverticular disease (DD) in patients with uncomplicated and complicated DD were reviewed by a scientific board of experts who proposed 55 statements graded according to level of evidence and strength of recommendation, and approved by an independent jury. Each topic was explored focusing on the more relevant clinical questions. Comparison and discussion of expert opinions, pertinent statements and replies to specific questions, were presented and approved based on a systematic literature search of the available evidence. Comments were added explaining the basis for grading the evidence, particularly for controversial areas.
| S-EPMC4212498 | biostudies-other
Project description:Background and Objectives: Diverticulosis affects a significant portion of the elderly population, with age and lifestyle being established risk factors. Additionally, genetic predisposition is gaining recognition as a contributing factor. This pilot study sought to explore the frequency of genetic variants in matrix metalloproteinases (MMPs) 3, 9, and 12 in a population of colonic diverticulosis patients. Materials and Methods: The study encompassed 134 participants: 59 diagnosed with colon diverticulosis during colonoscopy and 75 healthy controls. The cases and controls were meticulously matched in terms of age and gender. We assessed the distribution of genetic variants MMP3 rs3025058, MMP9 rs3918242, and MMP12 rs2276109 using the polymerase chain reaction-restriction fragments length polymorphism technique. Results: The MMP9 rs3918242 allele T was notably more frequent in individuals with diverticulosis when compared with the control group (p < 0.03). Furthermore, it was associated with dominant (OR = 2.62; 95% CI: 1.24-5.56; p < 0.01) and co-dominant (OR = 2.10; 95% CI: 1.06-4.13; p < 0.03) genetic models. The MMP3 rs3025058 5A/5A genotype was nearly twice as frequent in patients with diverticulosis, while the 6A/6A genotype was only half as common in this group. Conversely, no significant correlation was established between MMP12 rs2276109 and colonic diverticulosis. Conclusions: Our study offers the first insight into a potential connection between genetic variants in MMPs and colon diverticulosis. Specifically, allele T of MMP9 rs3918242 and allele 5A of MMP3 rs3025058 appear to be linked to this condition. These findings indirectly suggest a role for extracellular matrix proteins in the pathogenesis of diverticulosis.
| S-EPMC10673370 | biostudies-literature
Project description:Colonic diverticula are protrusions of the mucosa through weak areas of the colonic musculature. The etiology of diverticulosis is poorly understood, but could be related to gut bacteria. Using mucosal biopsies from the sigmoid colon of 226 subjects with and 309 subjects without diverticula during first-time screening colonoscopy, we assessed whether individuals with incidental colonic diverticulosis have alternations in the adherent bacterial communities in the sigmoid colon. We found little evidence of substantial associations between the microbial community and diverticulosis among cases and controls. Comparisons of bacterial abundances across all taxonomic levels showed differences for phylum Proteobacteria (p?=?0.038) and family Comamonadaceae (p?=?0.035). The r-squared values measuring the strength of these associations were very weak, however, with values ~2%. There was a similarly small association between the abundance of each taxa and total diverticula counts. Cases with proximal only diverticula and distal only diverticula likewise showed little difference in overall microbiota profiles. This large study suggests little association between diverticula and the mucosal microbiota overall, or by diverticula number and location. We conclude that the mucosal adherent microbiota community composition is unlikely to play a substantial role in development of diverticulosis.
| S-EPMC5862835 | biostudies-literature
Project description:BackgroundColonic diverticular disease is a bothersome condition with an unresolved pathogenesis. It is unknown whether a neuroepithelial dysfunction is present. The aim of the study was two-fold; (1) to investigate colonic epithelial ion transport in patients with diverticulosis and (2) to adapt a miniaturized Modified Ussing Air-Suction (MUAS) chamber for colonic endoscopic biopsies.MethodsBiopsies were obtained from the sigmoid part of the colon. 86 patients were included. All patients were referred for colonoscopy on suspicion of neoplasia and they were without pathological findings at colonoscopy (controls) except for diverticulosis in 22 (D-patients). Biopsies were mounted in MUAS chambers with an exposed area of 5 mm2. Electrical responses to various stimulators and inhibitors of ion transport were investigated together with histological examination. The MUAS chamber was easy to use and reproducible data were obtained.ResultsMedian basal short circuit current (SCC) was 43.8 microA x cm(-2) (0.8 - 199) for controls and 59.3 microA x cm(-2) (3.0 - 177.2) for D-patients. Slope conductance was 77.0 mS x cm(-2) (18.6 - 204.0) equal to 13 Omega x cm(2) for controls and 96.6 mS x cm(-2) (8.4 - 191.4) equal to 10.3 Omega x cm(2) for D-patients. Stimulation with serotonin, theophylline, forskolin and carbachol induced increases in SCC in a range of 4.9 - 18.6 microA x cm(-2), while inhibition with indomethacin, bumetanide, ouabain and amiloride decreased SCC in a range of 6.5 - 27.4 microA x cm(-2), and all with no significant differences between controls and D-patients. Histological examinations showed intact epithelium and lamina propria before and after mounting for both types of patients.ConclusionWe conclude that epithelial ion transport is not significantly altered in patients with diverticulosis and that the MUAS chamber can be adapted for studies of human colonic endoscopic biopsies.
| S-EPMC2064914 | biostudies-literature
Project description:The aim of this study was to determine the prevalence of colonic diverticulosis in mainland China. Sixty two thousand and thirty-four colonoscopies performed between Jan 2004 and Dec 2014 were reviewed retrospectively. The overall diverticulosis prevalence was 1.97% and out of this, 85.3% was right-sided. Prevalence does not change, significantly, on trends between the period 2004-2014. The peak of prevalence of diverticulosis was compared between the female group aged >70 years to the male one of 41-50 years. The other peak, otherwise, was compared between the group of 51-60 years with the right-sided diverticulosis to the one of >70 years with left-sided disease. Multivariate analysis suggested that the male gender could be a risk factor for diverticulosis in the group aged ≤70 years, but not for the older patients. In addition, among men was registered an increased risk factor for right-sided diverticulosis and, at the same time, a protective one for left-sided localization. In conclusion, the prevalence of colonic diverticulosis is very low in mainland China and it does not change significantly on trends over the time. Both the prevalence of this condition and its distribution changes according to the age and the genders. These findings may lead the researchers to investigate the mechanisms causing this kind of disease and its distribution in regard of the age and the gender.
| S-EPMC4869033 | biostudies-other
Project description:Diverticulosis results from complex interactions related to aging, environmental factors and genetic predisposition. Despite epidemiologic evidence of genetic risk factors, there has been no attempt to identify genes that confer susceptibility to colonic diverticulosis. We performed the first genome-wide association study (GWAS) on susceptibility to diverticulosis in a Korean population. A GWAS was carried out in 7,948 healthy individuals: 893 patients and 1,075 controls comprised the test set, and 346 patients and 305 controls comprised the replication set. Diverticulosis was diagnosed by colonoscopy during comprehensive medical check-ups, and single-nucleotide polymorphisms (SNPs) related to diverticulosis were detected with the Affymetrix Axiom KORV1.1-96 Array. In all, 9 SNPs were identified in three SNP aggregates in the test set (P < 10-3, within 200 kb) after adjusting for sex. All the SNPs were replicated in the replication set (P < 0.05). Three SNPs were near the WNT4 gene, four near the RHOU gene, and two in the OAS1/3 genes. The top SNP associated with right-sided colonic diverticulosis was rs22538787, located near the WNT4 gene [combined set, P-value = 3.128 × 10-6, odds ratio = 1.415 (95% confidence interval: 1.223-1.637)]. These 9 novel SNP alleles associated with the WNT4, RHOU, and OAS1/3 genes are possibly involved in the underlying genetic susceptibility to right-sided diverticulosis. Our results provide basic knowledge about the development of diverticulosis in an Asian population.
| S-EPMC6517584 | biostudies-literature