The Role of Zinc, Inflammation and Duodenal Mucosal Integrity in Cholesterol Gallstone Diseases

Introduction: Cholesterol Gallstone (GSD) is a common multifactorial disease characterized by an aggregation and growth of cholesterol crystals in the gallbladder. The global prevalence of GSD is ˜10-20% in adult population, but in Chile it rises to 28%, 17% men and 30% women, respectively. The small intestine have been identified contribute of developing gallstone, however, the molecular mechanism of the small intestine in the GSD pathogenesis have been poorly studied. Therefore, our aim was to identify the molecular mechanism of small intestine in GSD subject. Methods: Duodenal biopsy samples were obtained from patients with GSD and healthy volunteers. Presence or absence GSD was defined by abdominal ultrasonography. We performed transcriptome studies using the Illumina HiSeq 2500. We used real time PCR and immunofluorescence to validate the differentially expressed genes identified in GSD subjects. For identify number of intraepithelial lymphocytes and lysozymes expression were assessed by immunohistochemistry and immunofluorescence, respectively. Results: We identified 548 differentially expressed genes in GSD compared with control subjects. We observed enriched biological process related to cellular response to zinc, immune and antimicrobial responses, epithelial tube morphogenesis, apoptosis, DNA replication, and phospholipid metabolic process. Patients with GSD showed lower metallothionein and NPC1L1 expression, zinc level and tight junction gene expression, in change, an increased in immune and antimicrobial genes. A significant association between the zinc level and phytosterol concentration were observed. Conclusion: We identify for the first time that upper small intestine of GSD subjects have altered the zinc level, immune and antimicrobial responses and duodenal barrier function. These evidences allow us to hypothesize that the small intestine may have a key impact in GSD pathogenesis. Acknowledgment: Funded by FONDECYT 3160400. FONDAP Center for Genome Regulation 15090007.