Genetic Variants in Matrix Metalloproteinases <i>MMP3</i> (rs3025058) and <i>MMP9</i> (rs3918242) Associated with Colonic Diverticulosis

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 p p 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

Serotonin Metabolism and Serotonin Receptors Expression Are Altered in Colon Diverticulosis

Background and Objectives: Diverticulosis is frequently accompanied by altered bowel habits. The biogenic amines within colonic mucosa control bowel motility, and in particular, alterations in serotonin signaling may play a role in colon diverticulosis. The aim of the study was to assess the concentration of biogenic amines and serotonin receptor expression in the colonic mucosa in patients with diverticulosis and healthy controls. Materials and Methods: This prospective, comparative study included 59 individuals: 35 with sigmoid diverticulosis and 24 healthy controls. The study was held at the Department of Gastroenterology and Internal Medicine, Medical University of Warsaw, Poland. Mucosal samples were taken from the right and left colon during a colonoscopy in all patients. Concentrations of norepinephrine, 3-methoxy-4-hydroxyphenylglycol, dopamine, homovanillic acid, serotonin, and 5-hydroxyindoleacetic acid were measured with high-performance liquid chromatography. Expressions of human 5-hydroxytryptamine receptor 3A, 5-hydroxytryptamine receptor 4, 5-hydroxytryptamine receptor 7, solute carrier family 6 member 4 (SERT) for serotonin, as well as the neuroglia activation markers glial fibrillary acidic protein, S100 calcium-binding protein B, and proteolipid protein 1, were assessed with polymerase chain reaction. Results: The median age and sex distribution were comparable in both study groups (median 69 y vs. 52 y; p p p SERT expression was lower in the affected left segment compared to the right colon (median 0.88 vs. 1.36; p p -hydroxyindoleacetic acid/serotonin ratio (median 0.27 vs. 0.47; p Conclusions: The concentration of serotonin in the mucosa of the colon segment affected by diverticula is higher than in the healthy segment in the same individuals and higher than in healthy controls. These results underline serotonin signaling in colon diverticulosis pathophysiology