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

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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, José Luis
dc.contributor.authorPuschel, Klaus
dc.contributor.authorBambs, Claudia
dc.contributor.authorRoa, Juan Carlos
dc.contributor.authorGutiérrez, Rodrigo A.
dc.contributor.authorHampe, Jochen
dc.contributor.authorDe Ferrari, Giancarlo V.
dc.contributor.authorMiquel, Juan Francisco
dc.date.accessioned2024-07-11T17:11:47Z
dc.date.available2024-07-11T17:11:47Z
dc.date.issued2019-12-01
dc.descriptionIndexación: Scopus.
dc.description.abstractLatin 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.
dc.description.urihttps://www.nature.com/articles/s41598-018-35852-z
dc.identifier.citationScientific Reports Volume 9, Issue 1 1 December 2019 Article number 772
dc.identifier.doi10.1038/s41598-018-35852-z
dc.identifier.issn2045-2322
dc.identifier.urihttps://repositorio.unab.cl/handle/ria/58408
dc.language.isoen_US
dc.publisherNature Publishing Group
dc.rights.licenseATRIBUCIÓN 4.0 INTERNACIONAL
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/deed.es
dc.subjectAdult
dc.subjectAged
dc.subjectATP Binding Cassette Transporter, Subfamily G, Member 8
dc.subjectChile
dc.subjectCholecystectomy
dc.subjectDown-Regulation
dc.subjectDuodenum
dc.subjectEuropean Continental Ancestry Group
dc.subjectFemale
dc.subjectGallbladder
dc.subjectGallbladder Neoplasms
dc.subjectGallstones
dc.subjectGenetic Predisposition to Disease
dc.subjectGenome-Wide Association Study
dc.subjectHumans
dc.subjectIndians, South American
dc.subjectMale
dc.subjectMiddle Aged
dc.subjectPolymorphism, Single Nucleotide
dc.subjectTNF Receptor-Associated Factor 3
dc.subjectUltrasonography
dc.titleVariants in ABCG8 and TRAF3 genes confer risk for gallstone disease in admixed Latinos with Mapuche Native American ancestry
dc.typeArtículo
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