Common variants in ABCG8 and TRAF3 genes confer risk for gallstone disease and gallbladder cancer in admixed Latinos with Mapuche Native American ancestry

Simple item page
dc.catalogadoraba
dc.contributor.authorBustos, Bernabé I.
dc.contributor.authorPérez Palma, Eduardo
dc.contributor.authorBuch, Stephan
dc.contributor.authorAzócar, Lorena
dc.contributor.authorRiveras, Eleodoro
dc.contributor.authorUgarte, Giorgia D.
dc.contributor.authorToliat, Mohammad
dc.contributor.authorNürnberg, Peter
dc.contributor.authorLieb, Wolfgang
dc.contributor.authorFranke, Andre
dc.contributor.authorHinz, Sebastian
dc.contributor.authorBurmeister, Greta
dc.contributor.authorvon Schönfels, Witigo
dc.contributor.authorSchafmayer, Clemens
dc.contributor.authorVölzke, Henry
dc.contributor.authorVölker, Uwe
dc.contributor.authorHomuth, Georg
dc.contributor.authorLerch, Markus M.
dc.contributor.authorSantos Martín, José Luis
dc.contributor.authorPuschel Illanes, Klaus
dc.contributor.authorBambs S., Claudia
dc.contributor.authorGutiérrez Ilabaca, Rodrigo Antonio
dc.contributor.authorHampe, Jochen
dc.contributor.authorde Ferrari, Giancarlo V.
dc.contributor.authorMiquel, Juan Francisco
dc.date.accessioned2024-01-17T19:36:09Z
dc.date.available2024-01-17T19:36:09Z
dc.date.issued2018
dc.description.abstractBackground Latin Americans and Chilean Amerindians have the highest prevalence of cholesterol 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 population-attributable risk of the disease.Methods We performed a genome-wide association study (GWAS) for GSD in 1,095 admixed Latinos with Mapuche Native American Ancestry, followed by a replication analysis of 10 candidate single nucleotide polymorphisms (SNPs) with suggestive genome-wide significance (P<1×10−5) in 1,643 individuals. Disease status was assessed by cholecystectomy or abdominal ultrasonography. Logistic regression analyses were adjusted for age, sex, BMI, Type 2 Diabetes and Amerindian ancestry. Associated variants were further examined in two large GSD European populations and in a Chilean gallbladder cancer (GBC) cohort. We determined the expression levels of a novel GSD-candidate gene in normal and GSD-tissue samples.Results We consistently replicated the ABCG8 gene (rs11887534; P=3.24×10−8, OR=1.74) associated with GSD in admixed Latinos and identified a novel candidate signal within the TRAF3 gene on chromosome 14 (rs12882491; P=1.11×10−7, OR=1.40). ABCG8 and TRAF3 variants also conferred risk to GBC. Gene expression analyses indicated that TRAF3 levels were significantly decreased in the gallbladder (P=0.015) and the duodenal mucosa (P=0.001) of affected GSD individuals compared to healthy controls.Conclusions We confirmed ABCG8 and identified TRAF3 both associated with GSD and GBC in admixed Latinos. Decreased TRAF3 expression levels could enhance gallbladder inflammation as is observed in GSD and GSD-associated GBC.
dc.fechaingreso.objetodigital2024-01-19
dc.format.extent30 páginas
dc.fuente.origenORCID-ene24
dc.identifier.doi10.1101/265728
dc.identifier.urihttps://doi.org/10.1101/265728
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/80594
dc.information.autorucEscuela de Medicina; Santos Martín, José Luis; 0000-0003-2895-0369; 1005923
dc.information.autorucEscuela de Medicina; Puschel Illanes, Klaus; 0000-0002-1362-1311; 83957
dc.information.autorucEscuela de Medicina; Bambs S., Claudia; 0000-0002-7043-6833; 89631
dc.information.autorucFacultad de Ciencias Biológicas; Gutiérrez Ilabaca, Rodrigo Antonio; 0000-0002-5961-5005; 86782
dc.language.isoen
dc.nota.accesoContenido completo
dc.pagina.final30
dc.pagina.inicio1
dc.revistabioRxiv
dc.rightsacceso abierto
dc.rights.licenseCC BY-NC-ND 4.0 DEEDAttribution-NonCommercial-NoDerivs 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.ddc610
dc.subject.deweyMedicina y saludes_ES
dc.titleCommon variants in ABCG8 and TRAF3 genes confer risk for gallstone disease and gallbladder cancer in admixed Latinos with Mapuche Native American ancestry
dc.typepreprint
sipa.codpersvinculados1005923
sipa.codpersvinculados83957
sipa.codpersvinculados89631
sipa.codpersvinculados86782
sipa.trazabilidadORCID;2024-01-08
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
265728v2.full_Common variants in ABCG8 and TRAF3 genes confer.pdf
Size:
1.52 MB
Format:
Adobe Portable Document Format
Description:
Download
Collections
Artículos de revistas