Development of a Polygenic Risk Score to Predict Diverticulitis.

BACKGROUND: Despite its prevalence and associated morbidity, we remain limited in our ability to predict the course of a patient with diverticular disease. Although several clinical and genetic risk factors have been identified, we do not know how these factors relate to one another. OBJECTIVE: Our aim was to determine whether a polygenic risk score could improve risk prediction for diverticulitis and recurrent diverticulitis compared with a model using only clinical factors. DESIGN: This is an observational study. SETTING: The study examines the predictive ability of a polygenic risk score for diverticulitis developed using prior genome-wide association studies and validated using the MyCode biobank. PATIENTS: This study included patients of European ancestry in the Geisinger Health System who were enrolled in the MyCode Community Health biobanking program. MAIN OUTCOME MEASURES: The ability of a polygenic risk score to predict diverticulosis, diverticulitis, and recurrent diverticulitis was the main outcome measure of this study. RESULTS: A total of 60,861 patients were included, of whom 9912 (16.3%) had diverticulosis or diverticulitis (5015 with diverticulosis and 4897 with diverticulitis). When divided into deciles, our polygenic risk score stratified patients by risk of both diverticulosis and diverticulitis with a 2-fold difference in disease risk between the highest and lowest deciles for diverticulitis and a 4.8-fold difference for recurrent complicated diverticulitis. When compared with clinical factors alone, our polygenic risk score was able to improve risk prediction of recurrent diverticulitis. LIMITATIONS: Our population is largely located in a single geographic region and were classified by disease status, using international classification of diseases codes. CONCLUSIONS: This predictive model stratifies patients based on genetic risk for diverticular disease. The increased frequency of recurrent disease in our high-risk patients suggests that a polygenic risk score, in addition to other factors, may help guide the discussion regarding surgical intervention. See Video Abstract . DESARROLLO DE UNA PUNTUACIN DE RIESGO POLIGNICO PARA PREDECIR LA DIVERTICULITIS: ANTECEDENTES:A pesar de su prevalencia y morbilidad asociada, nuestra capacidad para predecir el curso en un paciente con enfermedad diverticular sigue siendo limitada. Si bien se han identificado varios factores de riesgo clínicos y genéticos, no sabemos cómo se relacionan estos factores entre sí.OBJETIVO:Determinar si una puntuación de riesgo poligénico podría mejorar la predicción del riesgo de diverticulitis y diverticulitis recurrente en comparación con un modelo que utiliza solo factores clínicos.DISEÑO:Un estudio observacional que examina la capacidad predictiva de una puntuación de riesgo poligénico para la diverticulitis desarrollada usando estudios previos de asociación amplia del genoma y validada usando el biobanco MyCode.ÁMBITOS Y PACIENTES:Pacientes de ascendencia europea en el Sistema de Salud Geisinger que estaban inscritos en el programa de biobancos MyCode Community Health.PRINCIPALES MEDIDAS DE VALORACIÓN:La capacidad de una puntuación de riesgo poligénico para predecir diverticulosis, diverticulitis y diverticulitis recurrente.RESULTADOS:Se incluyeron un total de 60.861 pacientes, de los cuales 9.912 (16,3%) presentaban diverticulosis o diverticulitis (5.015 con diverticulosis y 4.897 con diverticulitis). Cuando se dividió en deciles, nuestra puntuación de riesgo poligénico estratificó a los pacientes según el riesgo de diverticulosis y diverticulitis con una diferencia de 2 veces en el riesgo de enfermedad entre los deciles más alto y más bajo para diverticulitis y una diferencia de 4,8 veces para diverticulitis complicada recurrente. En comparación con los factores clínicos solos, nuestra puntuación de riesgo poligénico pudo mejorar la predicción del riesgo de diverticulitis recurrente.LIMITACIONES:Nuestra población se encuentra en gran parte en una sola región geográfica y se clasificó por estado de enfermedad utilizando códigos de clasificación internacional de enfermedades.CONCLUSIONES:Este modelo predictivo estratifica a los pacientes en función del riesgo genético de enfermedad diverticular. La mayor frecuencia de enfermedad recurrente en nuestros pacientes de alto riesgo sugiere que un puntaje de riesgo poligénico, además de otros factores, puede ayudar a guiar la discusión sobre la intervención quirúrgica. (Traducción- Dr. Ingrid Melo ).

Evaluation of molecular and genetic predisposing parameters at diverticular disease of the colon.

BACKGROUND: Diverticular disease (DD) refers to the presence of diverticula throughout the gastrointestinal (GI) tract, mainly along colon. DD might evolve into diverticulitis that is accompanied by severe clinical presentation, which includes abscess formation, perforation, stricture, obstruction and/or fistula. AIM: The aim of the present review is to summarize the role of molecular and genetic factors in DD development, as well as their possible contribution towards new prognostic indicators, diagnostic algorithms and new therapeutic approaches. METHODS AND RESULTS: Except from common predisposing parameters, several genetic mutations, immune factors, neurotransmitters, hormones and protein dysfunctions have been associated to the early onset of DD symptoms, pathogenesis and prognosis of the disease. Specific structural changes in the colonic wall, altered matrix composition and compromised motility have been verified as possible pathogenic factors for the development of DD. Dysregulation in peristaltic activity and reduced ability of the longitudinal muscle to relax following contraction has been also associated with DD evolution. In addition, it has been suspected that genetic defects combined with alterations in intestinal microbiota might play an important role in diverticulitis presentation.

AGA Clinical Practice Update on Medical Management of Colonic Diverticulitis: Expert Review.

Colonic diverticulitis is a painful gastrointestinal disease that recurs unpredictably and can lead to chronic gastrointestinal symptoms. Gastroenterologists commonly care for patients with this disease. The purpose of this Clinical Practice Update is to provide practical and evidence-based advice for management of diverticulitis. We reviewed systematic reviews, meta-analyses, randomized controlled trials, and observational studies to develop 14 best practices. In brief, computed tomography is often necessary to make a diagnosis. Rarely, a colon malignancy is misdiagnosed as diverticulitis. Whether patients should have a colonoscopy after an episode of diverticulitis depends on the patient's history, most recent colonoscopy, and disease severity and course. In patients with a history of diverticulitis and chronic symptoms, alternative diagnoses should be excluded with both imaging and lower endoscopy. Antibiotic treatment can be used selectively rather than routinely in immunocompetent patients with mild acute uncomplicated diverticulitis. Antibiotic treatment is strongly advised in immunocompromised patients. To reduce the risk of recurrence, patients should consume a high-quality diet, have a normal body mass index, be physically active, not smoke, and avoid nonsteroidal anti-inflammatory drug use except aspirin prescribed for secondary prevention of cardiovascular disease. At the same time, patients should understand that genetic factors also contribute to diverticulitis risk. Patients should be educated that the risk of complicated diverticulitis is highest with the first presentation. An elective segmental resection should not be advised based on the number of episodes. Instead, a discussion of elective segmental resection should be personalized to consider severity of disease, patient preferences and values, as well as risks and benefits.

Common variation in FAM155A is associated with diverticulitis but not diverticulosis.

Colonic diverticulosis is a very common condition. Many patients develop diverticulitis or other complications of diverticular disease. Recent genome-wide association studies (GWAS) consistently identified three major genetic susceptibility factors for both conditions, but did not discriminate diverticulititis and diverticulosis in particular due the limitations of registry-based approaches. Here, we aimed to confirm the role of the identified variants for diverticulosis and diverticulitis, respectively, within a well-phenotyped cohort of patients who underwent colonoscopy. Risk variants rs4662344 in Rho GTPase-activating protein 15 (ARHGAP15), rs7609897 in collagen-like tail subunit of asymmetric acetylcholinesterase (COLQ) and rs67153654 in family with sequence similarity 155 A (FAM155A) were genotyped in 1,332 patients. Diverticulosis was assessed by colonoscopy, and diverticulitis by imaging, clinical symptoms and inflammatory markers. Risk of diverticulosis and diverticulitis was analyzed in regression models adjusted for cofactors. Overall, the variant in FAM155A was associated with diverticulitis, but not diverticulosis, when controlling for age, BMI, alcohol consumption, and smoking status (ORadjusted 0.49 [95% CI 0.27-0.89], p = 0.002). Our results contribute to the assessment specific genetic variants identified in GWAS in the predisposition to the development of diverticulitis in patients with diverticulosis.

Etiopathogenetic Mechanisms in Diverticular Disease of the Colon.

This article reviews epidemiological evidence of heritability and putative mechanisms in diverticular disease, with greatest attention to 3 recent studies of genetic associations with diverticular disease based on genome-wide or whole-genome sequencing studies in large patient cohorts. We provide an analysis of the biological plausibility of the significant associations with gene variants reported and highlight the relevance of ANO1, CPI-17 (aka PPP1R14A), COLQ6, COL6A1, CALCB or CALCA, COL6A1, ARHGAP15, and S100A10 to colonic neuromuscular function and tissue properties that may result in altered compliance and predispose to the development of diverticular disease. Such studies also identify candidate genes for future studies.

Multifocal Versus Conventional Unifocal Diverticulitis: A Comparison of Clinical and Transcriptomic Characteristics.

BACKGROUND: The management of diverticulitis is compromised by difficulty in identifying patients who require surgery for recurrent or persistent disease. Here, we introduce the concept of multifocal diverticulitis (MFD), characterized by multiple episodes of diverticulitis occurring at different locations within the colon. AIMS: To compare clinical characteristics, success of surgical management, and colonic transcriptomes of MFD patients to patients with conventional unifocal diverticulitis (UFD). METHODS: This retrospective study included 404 patients with CT-confirmed diverticulitis episodes. Patients with diverticulitis seen in at least two different colonic locations were classified as the MFD group and compared to the UFD group based on number of episodes, sites of disease, family history, surgeries performed, and postoperative recurrence. RNA-seq was conducted on full-thickness colonic tissues of ten MFD and 11 UFD patients. RESULTS: Twenty-eight patients (6.9%) with MFD were identified. MFD patients had more diverticulitis episodes and were more likely to have positive family history, have right-sided disease, require surgery, and have recurrence after surgery. All MFD patients treated with segmental resection had recurrence, while recurrence was less common in patients undergoing more extensive surgery (P < 0.001). Using RNA-seq, we identified 69 genes that were differentially expressed between MFD and UFD patients. Significantly down-regulated genes were associated with immune response pathways. CONCLUSIONS: MFD appears to be a more severe subset of diverticulitis with a possible genetic component. Transcriptomic data suggest that MFD may be associated with alteration of the immune response.

A differential host response to viral infection defines a subset of earlier-onset diverticulitis patients.

BACKGROUND AND AIMS: Diverticulitis is the chronic inflammation of diverticula. Whether the pathophysiology of earlier-onset patients differs from later-onset patients is unknown. We profiled the colonic transcriptomes of these two patient populations to gain insight into the molecular underpinnings of diverticulitis. METHODS: We conducted deep RNA sequencing (RNA-seq) on colonic segments surgically resected from earlier-onset (<42 years old, n=13) and later-onset (>65 years old, n=13) diverticulitis patients. We used bioinformatic approaches to cluster the patients based on the relationship of differentially expressed genes and to inform on the molecular pathways that segregated the clusters. RESULTS: Principal component analysis identified three patient clusters; diverticulitis later-onset (DVT-LO), diverticulitis mixed-onset (DVT-MO), and diverticulitis earlier-onset (DVT-EO). The patients comprising DVT-EO, which was the majority of earlier-onset patients, displayed increased expression of anti-viral response genes. This finding was confirmed using an independent weighted co-expression network analysis (WGCNA) of differentially expressed genes. CONCLUSIONS: We found that the majority of patients with earlier-onset disease contained elevated expression of host genes involved in the anti-viral response. Thus, susceptibility to a viral pathogen may offer one explanation why some individuals develop diverticulitis at an earlier age.

Pathophysiology of diverticular disease.

INTRODUCTION: Inflammation of diverticula, or outpouchings of the colonic mucosa and submucosa through the muscularis layer, leads to diverticulitis. The development of diverticular disease, encompassing both diverticulosis and diverticulitis, is a result of genetic predisposition, lifestyle, and environmental factors, including the microbiome. Areas covered: Previous reports implicated genetic predisposition, environmental factors, and colonic dysmotility in diverticular disease. Recent studies have associated specific host immune responses and the microbiome as contributors to diverticulitis. To review pertinent literature describing pathophysiological factors associated with diverticulosis or diverticulitis, we searched the PubMed database (March 2018) for articles considering the role of colonic architecture, genetic predisposition, environment, colonic motility, immune response, and the microbiome. Expert commentary: In the recent years, research into the molecular underpinnings of diverticular disease has enhanced our understanding of diverticular disease pathogenesis. Although acute uncomplicated diverticulitis is treated with broad spectrum antibiotics, evaluation of the microbiome has been limited and requires further comprehensive studies. Evidence suggests that a deregulation of the host immune response is associated with both diverticulosis and diverticulitis. Further examining these pathways may reveal proteins that can be therapeutic targets or aid in identifying biological determinants of clinical or surgical decision making.

A Variant of COL3A1 (rs3134646) Is Associated With Risk of Developing Diverticulosis in White Men.

BACKGROUND: Colonic diverticulosis is one of the most common gastroenterological disorders. Although diverticulosis is typically benign, many individuals develop diverticulitis or other aspects of diverticular disease. Diverticulosis is thought to stem from a complex interaction of environmental, dietary, and genetic factors; however, the contributing genetic factors remain unknown. OBJECTIVE: The aim of our present study was to determine the role of genetic variants within genes encoding for collagens of the connective tissue in diverticulosis. DESIGN: This was a transsectional genetic association study. SETTINGS: This study was conducted at three tertiary referral centers in Germany and Lithuania. PATIENTS: Single-nucleotide polymorphisms in COL3A1 (rs3134646, rs1800255) and COL1A1 (rs1800012) were genotyped in 422 patients with diverticulosis and 285 controls of white descent by using TaqMan assays. MAIN OUTCOME MEASURES: The association of colonoscopy-proven diverticulosis with genetic polymorphisms with herniations was assessed in multivariate models. RESULTS: The rs3134646, rs1800255, and rs1800012 variants were significantly associated with the risk of developing diverticulosis in the univariate model; however, these associations were not significant in the multivariate logistic regression analysis including additional nongenetic variables. When selectively analyzing sexes, the genotype AA (AA) in rs3134646 remained significantly associated with diverticulosis in men (OR, 1.82; 95% CI, 1.04-3.20; p = 0.04). LIMITATIONS: Because a candidate approach was used, additional relevant variants could be missed. Within our cohort of patients with diverticulosis, only a small proportion had diverticular disease and thus, we could not examine the variants in these subgroups. Functional studies, including the analysis of the involved collagens, are also warranted. CONCLUSIONS: Our study shows that a variant of COL3A1 (rs3134646) is associated with the risk of developing colonic diverticulosis in white men, whereas rs1800255 (COL3A1) and rs1800012 (COL1A1) were not associated with this condition after adjusting for confounding factors. Our data provide novel valuable insights in the genetic susceptibility to diverticulosis. See Video Abstract at http://links.lww.com/DCR/A504.

Diverticulitis and Crohn's disease have distinct but overlapping tumor necrosis superfamily 15 haplotypes.

BACKGROUND: Diverticulitis (DD) and Crohn's disease (CD) have overlapping features including bowel structuring, inflammation, and infection. Tumor necrosis superfamily 15 (TNFSF15) is an immunoregulatory, anti-angiogenic gene. CD has been previously associated with a haplotype of five TNFSF15 single-nucleotide polymorphism alleles: rs3810936 (G allele), rs6478108 (A), rs6478109 (G), rs7848647 (G), and rs7869487 (A). We aimed to determine the TNFSF15 risk haplotype for DD versus controls with a subgroup analysis of youthful DD patients (aged ≤55 y) versus older controls (aged ≥55 y). METHODS: A total of 148 diverticulitis patients (90 aged ≤55 y) and 200 controls (87 aged ≥55 y) were genotyped using our custom-designed Illumina Veracode microarray chip. Genotypes from rs3810936, rs6478108, rs6478109, rs7848647, rs7869487 and two additional TNFSF15 single nucleotide polymorphisms, rs3810936 and rs11554257, were analyzed. PHASE version 2.1, R with HaploStats and the Broad Institute's Haploview program were used for statistics and imputed haplotype frequency. Permutation corrected for multiple comparisons. RESULTS: The CD GAGGA haplotype was significantly associated with diverticulitis (P = 0.03) in the all DD versus all controls comparison. A second haplotype, rs6478108 (A), rs6478109 (G), rs7869487 (A), and rs4263839 (G), was also associated with DD in this cohort (P = 0.025). A third haplotype rs6478108 (A), rs6478109 (G), rs7848647 (G) and rs7869487 (A), rs4263839 (G) was demonstrated in the DD < 55 versus controls >55 comparison (P = 0.045). CONCLUSIONS: Distinct but overlapping TNFSF15 haplotypes were demonstrated in diverticulitis patients versus healthy controls when compared with the known Crohn's risk haplotype suggesting similar but distinct genetic predispositions. This study strengthens the role for a genetic predisposition to diverticulitis that involves the TNFSF15 gene.

Folate Receptor-Beta Has Limited Value for Fluorescent Imaging in Ovarian, Breast and Colorectal Cancer.

AIMS: Tumor-specific targeted imaging is rapidly evolving in cancer diagnosis. The folate receptor alpha (FR-α) has already been identified as a suitable target for cancer therapy and imaging. FR-α is present on ~40% of human cancers. FR-ß is known to be expressed on several hematologic malignancies and on activated macrophages, but little is known about FR-ß expression in solid tumors. Additional or simultaneous expression of FR-ß could help extend the indications for folate-based drugs and imaging agents. In this study, the expression pattern of FR-ß is evaluated in ovarian, breast and colorectal cancer. METHODS: FR-ß expression was analyzed by semi-quantitative scoring of immunohistochemical staining on tissue microarrays (TMAs) of 339 ovarian cancer patients, 418 breast cancer patients, on 20 slides of colorectal cancer samples and on 25 samples of diverticulitis. RESULTS: FR-ß expression was seen in 21% of ovarian cancer samples, 9% of breast cancer samples, and 55% of colorectal cancer samples. Expression was weak or moderate. Of the diverticulitis samples, 80% were positive for FR-ß expression in macrophages. FR-ß status neither correlated to known disease-related variables, nor showed association with overall survival and progression free survival in ovarian and breast cancer. In breast cancer, negative axillary status was significantly correlated to FR-ß expression (p=0.022). CONCLUSIONS: FR-ß expression was low or absent in the majority of ovarian, breast and colorectal tumor samples. From the present study we conclude that the low FR-ß expression in ovarian and breast tumor tissue indicates limited practical use of this receptor in diagnostic imaging and therapeutic purposes. Due to weak expression, FR-ß is not regarded as a suitable target in colorectal cancer.

Surgical diverticulitis is not associated with defects in the expression of wound healing genes.

PURPOSE: The development of diverticuli may represent defects in collagen vascular tissue integrity possibly from a genetic predisposition. We evaluated the tissue expression of wound healing genes in sigmoid tissue from youthful patients undergoing surgery for diverticulitis and thus would more likely suffer from a genetic predisposition (SD mean age 39 ± 0.9) versus controls in the form of patients over the age of 50 (mean age 52.9 ± 10.5 years) without evidence of diverticular disease. METHODS: The mRNA expression of 84 genes associated with the extracellular matrix, cellular adhesion, growth factors, inflammatory cytokines, and signal transduction was evaluated in 16 SD and 15 control tissues using a Qiagen Wound Healing Array. Vitronectin, the gene protein with the highest potential significance on raw analysis, was further investigated using a Taqman assay with an additional 11 SD (total n = 27) and four control (total n = 19) samples. Statistics were by Student's t and Mann-Whitney tests with Bonferroni correction. RESULTS: No significant differences in mRNA expression between the SD and control tissue in the 84 measured genes were demonstrated after correction. Vitronectin mRNA expression was downregulated 2.7-fold in SD tissue vs. tissue from non-neoplastic control patients (p = 0.001 raw/0.08 corrected). However, on vitronectin TaqMan analysis, no difference in expression was seen in SD vs. all controls or in all subset comparisons. CONCLUSIONS: The lack of significant alteration in mRNA expression of traditionally associated wound healing genes/proteins in young SD patients suggests that such genes play a minor role in the genetic predisposition to youthful diverticulitis.

Expression of basic fibroblastic growth factor, syndecan 1 and tumour necrosis factor α in resected acute colonic diverticulitis.

AIM: Inflammation and fibrosis are present in both colonic diverticulitis and Crohn's disease (CD). The molecular pattern of basic fibroblastic growth factor (bFGF) and syndecan 1 (SD1) expression is altered in stenosing CD, but their expression in resected complicated colonic diverticulitis (ACD) is unknown. METHOD: The expression of bFGF, SD1 and tumour necrosis factor α (TNF-α) in 20 patients after resection of ACD was compared with 15 patients having a resection for CD. Analysis was conducted using real-time reverse transcriptase polymerase chain reaction in biopsy samples. RESULTS: Lymphocytic and neutrophil inflammation scores were similar in both groups (P = 0.771 and P = 0.562). TNF-α and bFGF expression was significantly higher in ACD than in CD (P < 0.0001 and P = 0.009). SD1 expression was similar in both groups (P = 0.841). CONCLUSION: TNF-α and bFGF are significantly overexpressed in ACD with respect to CD, whilst SD1 levels do not differ. The findings confirm that inflammation and its association with altered molecular patterns of mucosal healing may play an important role in the phenotype of the diseases.

Alterations of the enteric smooth musculature in diverticular disease.

BACKGROUND: The pathogenesis of diverticular disease (DD) is considered to be multifactorial and involves intestinal motor disturbances and an underlying enteric neuromuscular pathology. While an enteric neuropathy has been well documented, actual studies on concomitant alterations of the enteric musculature are limited. This study is aimed at reassessing the smooth muscle tissue by histological, ultrastructural and molecular-biological approaches. METHODS: Full-thickness sigmoid specimens were obtained from patients with DD (n = 20) and controls (n = 19). Morphometric analysis was performed to evaluate the thickness and connective tissue index of the circular and longitudinal muscle layers as well as the myenteric plexus. Structural alterations were determined by light and transmission electron microscopy. mRNA profiles of components of the contractile smooth muscle apparatus including smooth muscle α-actin, smoothelin, histone deacetylase 8, and smooth muscle myosin heavy chain (SMMHC) were assessed by qPCR. Altered gene expression levels were confirmed at protein level by immunohistochemistry. RESULTS: Compared to controls, patients with DD showed (1) increased thickness of the circular and longitudinal muscle layers, (2) architectural alterations of smooth muscle cells, (3) increased connective tissue index of the longitudinal muscle layer, (4) focally reduced density of myofilaments at ultrastructural level, (5) specific down-regulation of SMMHC mRNA levels, (6) decreased immunoreactivity of SMMHC, (7) oligo-neuronal hypoganglionosis. CONCLUSIONS: DD is associated with distinct structural and functional alterations of the enteric musculature. The enteric myopathy is characterized by disturbed muscular architecture, connective tissue replacement and loss of specific myofilaments and thus may contribute to the pathogenesis and progression of DD.

Colonic diverticulitis in adolescents: an index case and associated syndromes.

Diverticular disease of the colon, a common problem among adults, is diagnosed rarely in children. We report an adolescent patient with sigmoid diverticulitis who required operative treatment. Pediatric patients with the complications of diverticula typically have conditions that result in genetic alterations affecting the components of the colonic wall. Our patient had Williams-Beuren syndrome, although Ehlers-Danlos syndrome, Marfan syndrome, and cystic fibrosis may also be associated with colonic diverticula in adolescence. Pediatric patients with these disorders who experience abdominal pain should be evaluated for the presence of colonic diverticular complications.

Serotonin signaling in diverticular disease.

Diverticulosis is extremely common in Western societies and is associated with complications in up to 15%of cases. Altered motility is an important feature of the pathogenesis of diverticular disease, and serotonin (5-HT) release is a primary trigger of gut motility. This study aims to determine whether colonic 5-HT signaling is altered in patients with diverticulosis or diverticulitis, and whether differences in serotonin signaling may distinguish patients with asymptomatic diverticulosis from those who develop disease specific complications. Sigmoid colon biopsies were obtained from healthy control subjects, individuals with asymptomatic diverticulosis, and those with a history of CT-proven diverticulitis within the preceding 6 months. The key elements of 5-HT signaling including content, release, and 5-HT transporter (SERT) expression were analyzed. A significant decrease in SERT transcript levels was present in the mucosa of patients with a history of diverticulitis when compared with controls, but not in those with asymptomatic diverticulosis. Mucosal 5-HT content, enterochromaffin (EC) cell numbers, and TpH-1 mRNA levels were comparable amongst the groups, as were basal and stimulated 5-HT release. Alterations in 5-HT signaling do not appear to be responsible for the development of diverticula. However, patients with a recent history of acute diverticulitis have a significant attenuation in SERT expression and function, likely secondary to previous inflammation. Our findings may explain the persistent symptoms of pain and altered motility so often observed in patients with diverticulitis long after recovery from the acute inflammatory response.

Polimorfismo do exon 20 do gene da elastina em indivíduos portadores de doença diverticular dos cólons / Polymorphism of 20 of elastin gene in individuals with colonic diverticular disease

A doença diverticular dos cólons (DDC) é relacionada à dieta, pressão intraluminal elevada, bem como alterações estruturais da parede intestinal. Pacientes com alterações genéticas do gene da elastina (ELN), como a estenose aórtica supravalvar e a cútis laxa, podem manifestar hérnia, diverticulose e disfunção urinária. Recentemente, uma mutação pontual no exon 20 do ELN foi demonstrada em pacientes com hérnia inguinal. No presente estudo é demonstrada uma mutação pontual (AGTGGT) no códon 422 do exon 20 do ELN em 5/14 pacientes com DDC e em 0/26 controles. Foi observada uma associação significativa desta mutação com o desenvolvimento da DDC. /Colonic diverticular disease (CDD) is related to diet, increased intraluminal pressure and structural changes within intestinal wall. Patients carrying genetic disorders of elastin (ELN) gene, such as supravalvular aortic stenosis and cutis laxa, may present hernias, diverticulosis and bladder dysfunction. Recently, a punctual mutation in exon 20 of ELN gene was detected in patients with inguinal hernia. Present study demonstrates a punctual mutation (AGTGGT) within codon 422 of ELN gene in 5/14 patients carrying CDD and in 0/26 among controls. This investigation demonstrated a significant association between the mutation found and CDD development...