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Sterol transporter adenosine triphosphate-binding cassette transporter G8, gallstones, and biliary cancer in 62,000 individuals from the general population.
- Source :
-
Hepatology (Baltimore, Md.) [Hepatology] 2011 Feb; Vol. 53 (2), pp. 640-8. Date of Electronic Publication: 2010 Dec 28. - Publication Year :
- 2011
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Abstract
- Unlabelled: 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).<br />Conclusion: In this general population cohort, ABCG8 D19H genotype was an important predictor of both symptomatic gallstone disease and biliary cancer.<br /> (Copyright © 2010 American Association for the Study of Liver Diseases.)
- Subjects :
- ATP Binding Cassette Transporter, Subfamily G, Member 8
Aged
Aged, 80 and over
Alanine Transaminase blood
Bile Duct Neoplasms ethnology
Cholesterol, LDL blood
Denmark
Female
Follow-Up Studies
Gallstones ethnology
Genotype
Heterozygote
Homozygote
Humans
Incidence
Longitudinal Studies
Male
Middle Aged
Predictive Value of Tests
Retrospective Studies
Risk Factors
gamma-Glutamyltransferase blood
ATP-Binding Cassette Transporters genetics
Bile Duct Neoplasms epidemiology
Bile Duct Neoplasms genetics
Gallstones epidemiology
Gallstones genetics
Genetic Predisposition to Disease genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1527-3350
- Volume :
- 53
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Hepatology (Baltimore, Md.)
- Publication Type :
- Academic Journal
- Accession number :
- 21274884
- Full Text :
- https://doi.org/10.1002/hep.24046