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The ABCG5/8 cholesterol transporter and myocardial infarction versus gallstone disease.
MedLine Citation:
PMID:  24657701     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
OBJECTIVE: To test the hypothesis that genetic variation in ABCG5/8, the transporter responsible for intestinal and hepatobiliary cholesterol efflux, might simultaneously influence plasma and biliary cholesterol levels, and hence risk of myocardial infarction(MI) and gallstone disease in opposite directions.
BACKGROUND: High plasma levels of low-density lipoprotein(LDL) cholesterol are a causal risk factor for MI, whereas high levels of biliary cholesterol promote gallstone formation.
METHODS: A total of 60,239 subjects from Copenhagen were included, including 5,647 with MI and 3,174 with symptomatic gallstone disease. Subjects were genotyped for six common, nonsynonymous and functional variants in ABCG5/8, and a combined weighted genotype score was calculated.
RESULTS: Combined, weighted genotype scores were associated with stepwise decreases in LDL cholesterol of up to 5.9%(0.20 mmol/L) for individuals with a score ≥8.0 (prevalence=11%) versus <2.0 (prevalence=9%) (p for trend across five groups=2×10E-35). The cumulative incidences of myocardial infarction and gallstone disease as a function of age and increasing genotype score were, respectively, decreased and increased(log-rank p-trend: 6×10E-4 and 9×10E-45). The multifactorially adjusted odds ratios were 0.83(95% confidence interval, 0.73 to 0.94) for myocardial infarction and 2.85(2.39 to 3.39) for symptomatic gallstone disease for individuals with a genotype score ≥8.0 versus <2.0.
CONCLUSIONS: Genetic variation in ABCG5/8 which associates with decreased levels of plasma LDL cholesterol protects against myocardial infarction, but increases the risk of symptomatic gallstone disease. These results suggest that myocardial infarction and gallstones, two seemingly unrelated diseases, are intrinsically linked via the function of the ABCG5/8 cholesterol transporter.
Authors:
Stefan Stender; Ruth Frikke-Schmidt; Børge G Nordestgaard; Anne Tybjærg-Hansen
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-3-5
Journal Detail:
Title:  Journal of the American College of Cardiology     Volume:  -     ISSN:  1558-3597     ISO Abbreviation:  J. Am. Coll. Cardiol.     Publication Date:  2014 Mar 
Date Detail:
Created Date:  2014-3-24     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8301365     Medline TA:  J Am Coll Cardiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
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