| Association of loss-of-function mutations in the ABCA1 gene with high-density lipoprotein cholesterol levels and risk of ischemic heart disease. | |
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MedLine Citation:
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PMID: 18523221 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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CONTEXT: Low levels of high-density lipoprotein (HDL) cholesterol are inversely related to cardiovascular risk. Whether this is a causal effect is unclear. OBJECTIVE: To determine whether genetically reduced HDL cholesterol due to heterozygosity for 4 loss-of-function mutations in ABCA1 cause increased risk of ischemic heart disease (IHD). DESIGN, SETTING, AND PARTICIPANTS: Three studies of white individuals from Copenhagen, Denmark, were used: the Copenhagen City Heart Study (CCHS), a 31-year prospective general population study (n = 9022; 28 heterozygotes); the Copenhagen General Population Study (CGPS), a cross-sectional general population study (n = 31,241; 76 heterozygotes); and the Copenhagen Ischemic Heart Disease Study (CIHDS), a case-control study (n = 16,623; 44 heterozygotes). End points in all 3 studies were recorded during the period of January 1, 1976, through July 9, 2007. MAIN OUTCOME MEASURES: Levels of HDL cholesterol in the general population, cellular cholesterol efflux, and the association between IHD and HDL cholesterol and genotype. RESULTS: Heterozygotes vs noncarriers for 4 ABCA1 mutations (P1065S, G1216V, N1800H, R2144X) had HDL cholesterol levels of 41 mg/dL (interquartile range, 31-50 mg/dL) vs 58 mg/dL (interquartile range, 46-73 mg/dL), corresponding to a reduction in HDL cholesterol of 17 mg/dL (P < .001). A 17-mg/dL lower HDL cholesterol level in the CCHS was associated with a multifactorially adjusted hazard ratio for IHD of 1.70 (95% confidence interval [CI], 1.57-1.85). However, for IHD in heterozygotes vs noncarriers, the multifactorially adjusted hazard ratio was 0.67 (95% CI, 0.28-1.61; 1741 IHD events) in the CCHS, the multifactorially adjusted odds ratio was 0.82 (95% CI, 0.34-1.96; 2427 IHD events) in the CGPS, and the multifactorially adjusted odds ratio was 0.86 (95% CI, 0.32-2.32; 2498 IHD cases) in the CIHDS. The corresponding odds ratio for IHD in heterozygotes vs noncarriers for the combined studies (n = 41,961; 6666 cases; 109 heterozygotes) was 0.93 (95% CI, 0.53-1.62). CONCLUSION: Lower plasma levels of HDL cholesterol due to heterozygosity for loss-of-function mutations in ABCA1 were not associated with an increased risk of IHD. |
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Authors:
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Ruth Frikke-Schmidt; Børge G Nordestgaard; Maria C A Stene; Amar A Sethi; Alan T Remaley; Peter Schnohr; Peer Grande; Anne Tybjaerg-Hansen |
Publication Detail:
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Type: Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: JAMA : the journal of the American Medical Association Volume: 299 ISSN: 1538-3598 ISO Abbreviation: JAMA Publication Date: 2008 Jun |
Date Detail:
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Created Date: 2008-06-04 Completed Date: 2008-06-11 Revised Date: 2008-11-10 |
Medline Journal Info:
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Nlm Unique ID: 7501160 Medline TA: JAMA Country: United States |
Other Details:
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Languages: eng Pagination: 2524-32 Citation Subset: AIM; IM |
Affiliation:
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Department of Clinical Biochemistry, Rigshospitalet, Herlev Hospital. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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ATP-Binding Cassette Transporters
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genetics* Aged Cholesterol, HDL / blood* Denmark European Continental Ancestry Group / genetics Female Genotype Humans Loss of Heterozygosity Male Middle Aged Mutation* Myocardial Ischemia / blood*, epidemiology, genetics* Risk Factors |
| Chemical | |
Reg. No./Substance:
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0/ATP binding cassette transporter 1; 0/ATP-Binding Cassette Transporters; 0/Cholesterol, HDL |
| Comments/Corrections | |
Comment In:
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JAMA. 2008 Nov 5;300(17):1997-8; author reply 1998
[PMID:
18984885
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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