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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2011-1-28
pubmed:abstractText
Gallstone disease, a risk factor for biliary cancer, has a strong heritable component, but the underlying genes are largely unknown. To test the hypothesis that ABCG8 (adenosine triphosphate-binding cassette transporter G8) Asp19His (D19H) genotype predicted risk of gallstones and biliary cancer in the general population, we studied 62,279 white individuals from The Copenhagen City Heart Study and The Copenhagen General Population Study, randomly selected to reflect the adult Danish population aged 20 to 80+ years. Endpoints were recorded from January 1976 through May 2009. During a mean follow-up of, respectively, 31 and 4.4 years, 3124 participants developed symptomatic gallstone disease and 30 developed biliary cancer. The multifactorially adjusted hazard ratio for symptomatic gallstone disease was 1.9 (95% confidence interval, 1.7-2.1) in DH heterozygotes (prevalence, 12%), and 3.3 (2.3-4.6) in HH homozygotes (0.4%) versus noncarriers (P for trend <0.001). Mean age at onset of symptomatic gallstone disease was 56 years for noncarriers, 54 for DH heterozygotes, and 52 for HH homozygotes (P for trend <0.001). The fraction of all gallstones attributed to D19H was 11%. The multifactorially adjusted hazard ratio for biliary cancer was 4.0 (1.9-8.4) in DH heterozygotes and HH homozygotes combined versus noncarriers (P < 0.001). The fraction of all biliary cancers attributed to the D19H genotype was 27%. Finally, D19H genotype associated with stepwise increases in plasma levels of alanine aminotransferase and gamma glutamyltransferase of up to 14% and 25% in HH homozygotes, and with corresponding stepwise reductions in plasma levels of total and low-density lipoprotein cholesterol of up to 5% versus noncarriers (all comparisons, P for trend <0.001). CONCLUSION: In this general population cohort, ABCG8 D19H genotype was an important predictor of both symptomatic gallstone disease and biliary cancer.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1527-3350
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 American Association for the Study of Liver Diseases.
pubmed:issnType
Electronic
pubmed:volume
53
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
640-8
pubmed:meshHeading
pubmed-meshheading:21274884-ATP-Binding Cassette Transporters, pubmed-meshheading:21274884-Aged, pubmed-meshheading:21274884-Aged, 80 and over, pubmed-meshheading:21274884-Alanine Transaminase, pubmed-meshheading:21274884-Bile Duct Neoplasms, pubmed-meshheading:21274884-Cholesterol, LDL, pubmed-meshheading:21274884-Denmark, pubmed-meshheading:21274884-Female, pubmed-meshheading:21274884-Follow-Up Studies, pubmed-meshheading:21274884-Gallstones, pubmed-meshheading:21274884-Genetic Predisposition to Disease, pubmed-meshheading:21274884-Genotype, pubmed-meshheading:21274884-Heterozygote, pubmed-meshheading:21274884-Homozygote, pubmed-meshheading:21274884-Humans, pubmed-meshheading:21274884-Incidence, pubmed-meshheading:21274884-Longitudinal Studies, pubmed-meshheading:21274884-Male, pubmed-meshheading:21274884-Middle Aged, pubmed-meshheading:21274884-Predictive Value of Tests, pubmed-meshheading:21274884-Retrospective Studies, pubmed-meshheading:21274884-Risk Factors, pubmed-meshheading:21274884-gamma-Glutamyltransferase
pubmed:year
2011
pubmed:articleTitle
Sterol transporter adenosine triphosphate-binding cassette transporter G8, gallstones, and biliary cancer in 62,000 individuals from the general population.
pubmed:affiliation
Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't