Loci From a Genome-Wide Analysis of Bilirubin Levels Are Associated With Gallstone Risk and Composition

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dc.contributor.authorBuch, Stephan
dc.contributor.authorSchafmayer, Clemens
dc.contributor.authorVoelzke, Henry
dc.contributor.authorSeeger, Marcus
dc.contributor.authorMiquel, Juan F.
dc.contributor.authorSookoian, Silvia C.
dc.contributor.authorEgberts, Jan H.
dc.contributor.authorArlt, Alexander
dc.contributor.authorPirola, Carlos J.
dc.contributor.authorLerch, Markus M.
dc.contributor.authorJohn, Ulrich
dc.contributor.authorFranke, Andre
dc.contributor.authorvon Kampen, Oliver
dc.contributor.authorBrosch, Mario
dc.contributor.authorNothnagel, Michael
dc.contributor.authorKratzer, Wolfgang
dc.contributor.authorBoehm, Bernhard O.
dc.contributor.authorBroering, Dieter C.
dc.contributor.authorSchreiber, Stefan
dc.contributor.authorKrawczak, Michael
dc.contributor.authorHampe, Jochen
dc.date.accessioned2024-01-10T13:50:03Z
dc.date.available2024-01-10T13:50:03Z
dc.date.issued2010
dc.description.abstractBACKGROUND & AIMS: Genome-wide association studies have mapped loci that are associated with serum levels of bilirubin. Bilirubin is a major component of gallstones so we investigated whether these variants predict gallstone bilirubin content and overall risk for gallstones. METHODS: Loci that were identified in a meta-analysis to attain a genome-wide significance level of a P value less than 1.0 x 10(-7) (UGT1A1, SLCO1B1, LST-3TM12, SLCO1A2) were analyzed in 1018 individuals with known gallstone composition. Gallstone risk was analyzed in 2606 German choleystecomized individuals and 1121 controls and was replicated in 210 cases and 496 controls from South America. RESULTS: By using the presence of bilirubin as a phenotype, variants rs6742078 (UGT1A1; P = .003), rs4149056 (SLCO1B1; P = .003), and rs4149000 (SLCO1A2; P = .015) were associated with gallstone composition. In regression analyses, only UGT1A1 and SLCO1B1 were independently retained in the model. UGT1A1 (rs6742078; P = .018) was associated with overall gallstone risk. In a sex-stratified analysis, only male carriers of rs6742078 had an increased risk for gallstone disease (P = 2.1 x 10(-7); odds ratio(recessive), 2.34; P-women = .47). The sex-specific association of rs6742078 was confirmed in samples from South America (P-men = .046; odds ratio(recessive), 2.19; P-women = .96). CONCLUSIONS: The UGT1A1 Gilbert syndrome variant rs6742078 is associated with gallstone disease in men; further studies are required regarding the sex-specific physiology of bilirubin and bile acid metabolism. Variants of ABCG8 and UGT1A1 are the 2 major risk factors for overall gallstone disease, they contribute a population attributable risk of 21.2% among men.
dc.description.funderDeutsche Forschungsgemeinschaft
dc.description.funderGerman Ministry of Education and Research (BMBF) through the POPGEN Biobank
dc.description.funderBMBF
dc.description.funderMinistry for Education, Research, and Cultural Affairs
dc.description.funderMinistry for Social Affairs of the Federal State of Mecklenburg-Vorpommern
dc.description.funderCentre of Excellence Metabolic Disorders Baden-Wuerttemberg
dc.description.funderFondo Nacional Cientifico y Tecnologico
dc.fechaingreso.objetodigital2024-04-25
dc.format.extent12 páginas
dc.fuente.origenWOS
dc.identifier.doi10.1053/j.gastro.2010.09.003
dc.identifier.issn0016-5085
dc.identifier.pubmedidMEDLINE:20837016
dc.identifier.urihttps://doi.org/10.1053/j.gastro.2010.09.003
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/79501
dc.identifier.wosidWOS:000284843600033
dc.information.autorucMedicina; Miquel JF;S/I;72216
dc.issue.numero6
dc.language.isoen
dc.nota.accesocontenido parcial
dc.publisherW B SAUNDERS CO-ELSEVIER INC
dc.revistaGASTROENTEROLOGY
dc.rightsacceso restringido
dc.subjectPigment Gallstones
dc.subjectCholelithiasis
dc.subjectComplex Disease
dc.subjectANION-TRANSPORTING POLYPEPTIDE
dc.subjectMESSENGER-RNA EXPRESSION
dc.subjectGILBERTS-SYNDROME
dc.subjectCHOLESTEROL CHOLELITHIASIS
dc.subjectUNCONJUGATED BILIRUBIN
dc.subjectDISEASE
dc.subjectPOPULATION
dc.subjectLIVER
dc.subjectUGT1A1
dc.subjectPREVALENCE
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleLoci From a Genome-Wide Analysis of Bilirubin Levels Are Associated With Gallstone Risk and Composition
dc.typeartículo
dc.volumen139
sipa.codpersvinculados72216
sipa.indexWOS
sipa.indexScopus
sipa.trazabilidadCarga SIPA;09-01-2024
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