Variants in ABCG8 and TRAF3 genes confer risk for gallstone disease in admixed Latinos with Mapuche Native American ancestry.

Latin Americans and Chilean Amerindians have the highest prevalence of gallstone disease (GSD) and gallbladder cancer (GBC) in the world. A handful of loci have been associated with GSD in populations of predominantly European ancestry, however, they only explain a small portion of the genetic component of the disease. Here, we performed a genome-wide association study (GWAS) for GSD in 1,095 admixed Chilean Latinos with Mapuche Native American ancestry. Disease status was assessed by cholecystectomy or abdominal ultrasonography. Top-10 candidate variants surpassing the suggestive cutoff of P < 1 × 10-5 in the discovery cohort were genotyped in an independent replication sample composed of 1,643 individuals. Variants with positive replication were further examined in two European GSD populations and a Chilean GBC cohort. We consistently replicated the association of ABCG8 gene with GSD (rs11887534, P = 3.24 × 10-8, OR = 1.74) and identified TRAF3 (rs12882491, P = 1.11 × 10-7, OR = 1.40) as a novel candidate gene for the disease in admixed Chilean Latinos. ABCG8 and TRAF3 variants also conferred risk to GBC. Gene expression analyses indicated that TRAF3 was significantly decreased in gallbladder (P = 0.015) and duodenal mucosa (P = 0.001) of GSD individuals compared to healthy controls, where according to GTEx data in the small intestine, the presence of the risk allele contributes to the observed effect. We conclude that ABCG8 and TRAF3 genes are associated with GSD and GBC in admixed Latinos and that decreased TRAF3 levels could enhance gallbladder inflammation as is observed in GSD and GSD-associated GBC.

[Histopathological study of the presence of Helicobacter pylori-type bacteria in surgical specimens from patients with chronic cholecystitis]. / Estudio histopatológico de la presencia de bacterias tipo Helicobacter pylori en especímenes quirúrgicos con colecistitis crónica.

INTRODUCTION: Helicobacter species have recently been found to be associated with some diseases of the biliary tree but this relationship remains unclear and further studies are required. The aim of this study was to determine the presence of H. pylori-type bacteria in patients with a diagnosis of chronic cholecystitis through histopathological study of surgical gallbladder specimens. MATERIALS AND METHODS: Surgical gallbladder specimens from patients with a diagnosis of chronic cholecystitis were examined histopathologically. The macroscopic characteristics of the specimens were identified. Histopathological slices were stained with hematoxylin-eosin and Giemsa. RESULTS: Of the 68 patients who underwent cholecystectomy, 56 (81%) were women and 12 (19%) were men. The mean age was 39.56+11.94 years. H. pylori-type bacteria were found in 6%. CONCLUSIONS: The results of this study do not allow us to conclude that the presence of H. pylori-type bacteria is a major factor in the etiology and/or pathogenesis of chronic cholecystitis. In patients with chronic cholecystitis undergoing cholecystectomy included in the present study, the etiology of the disease may be more closely linked with the presence of gallstones.

Low serum levels of ghrelin are associated with gallstone disease.

AIM: To explore the role of ghrelin in gallstone disease. METHODS: We carried out a cross-sectional study in 150 subjects, 38 with gallstones (cases) and 112 controls. We also did a real-time PCR-RT study in twenty gallbladder samples each. Body mass index (BMI), serum insulin, ghrelin, and serum lipids were measured. Logistic regression analyses (univariate and multivariate) were conducted to estimate the probability of gallstone disease associated with serum ghrelin concentrations. RESULTS: Cases were statistically different from controls in gender distribution (P = 0.01), age (53 vs 44 yr, P = 0.002), BMI (28 vs 25; P = 0.004), and glucose (5.26 vs 4.98 mmol/L; P = 0.05). The prevalence of ghrelin serum levels above the third tercile was lower in subjects without metabolic syndrome (P < 0.05). In a multivariate model, we found a protective effect, when ghrelin values were higher than the median value (OR = 0.27, 95%CI 0.09-0.82, P = 0.02). Twenty (20%) gallbladder specimens expressed ghrelin mRNA. CONCLUSION: Serum ghrelin concentrations are associated with a protective effect of GD.

Value of CEA level determination in gallbladder bile in the diagnosis of liver metastases secondary to colorectal adenocarcinoma

CONTEXT: The relevance of colorectal adenocarcinoma lies in its high incidence, with the liver being the organ most frequently affected by distant metastases. Liver metastases occur in 40 to 50 percent of patients with colorectal adenocarcinoma, accounting for approximately 80 percent of deaths in the first three postoperative years. Nevertheless, despite this, they are occasionally susceptible to curative treatment. OBJECTIVE: The present investigation focused on the relationship between the level of carcinoembryonic antigen (CEA) in gallbladder bile and the presence of liver metastases secondary to colorectal adenocarcinoma. DESIGN: Diagnostic test study. SETTING: Surgical Gastroenterology Discipline at the Säo Paulo Hospital, Säo Paulo, Brazil. SAMPLE: Forty-five patients with colorectal adenocarcinoma were studied, 30 without liver metastases (group I), and 15 with liver metastases (group II). Diagnosis of liver metastases was made through computed tomography, magnetic resonance imaging and computed tomography during arterial portography. Samples of peripheral blood, portal system blood, and gallbladder bile were collected from patients during the surgical procedure. A control group composed of 18 organ donors underwent the same material collection procedures...