Show simple item record Chiba-Falek, O Nichols, M Suchindran, S Guyton, J Ginsburg, GS Barrett-Connor, E McCarthy, JJ
dc.coverage.spatial England 2011-06-21T17:29:34Z 2010-01-19
dc.identifier 1471-2350-11-9
dc.identifier.citation BMC Med Genet, 2010, 11 pp. 9 - ?
dc.description.abstract BACKGROUND: Several studies have noted that genetic variants of SCARB1, a lipoprotein receptor involved in reverse cholesterol transport, are associated with serum lipid levels in a sex-dependent fashion. However, the mechanism underlying this gene by sex interaction has not been explored. METHODS: We utilized both epidemiological and molecular methods to study how estrogen and gene variants interact to influence SCARB1 expression and lipid levels. Interaction between 35 SCARB1 haplotype-tagged polymorphisms and endogenous estradiol levels was assessed in 498 postmenopausal Caucasian women from the population-based Rancho Bernardo Study. We further examined associated variants with overall and SCARB1 splice variant (SR-BI and SR-BII) expression in 91 human liver tissues using quantitative real-time PCR. RESULTS: Several variants on a haplotype block spanning intron 11 to intron 12 of SCARB1 showed significant gene by estradiol interaction affecting serum lipid levels, the strongest for rs838895 with HDL-cholesterol (p=9.2x10(-4)) and triglycerides (p=1.3x10(-3)) and the triglyceride:HDL cholesterol ratio (p=2.7x10(-4)). These same variants were associated with expression of the SR-BI isoform in a sex-specific fashion, with the strongest association found among liver tissue from 52 young women<45 years old (p=0.002). CONCLUSIONS: Estrogen and SCARB1 genotype may act synergistically to regulate expression of SCARB1 isoforms and impact serum levels of HDL cholesterol and triglycerides. This work highlights the importance of considering sex-dependent effects of gene variants on serum lipid levels.
dc.format.extent 9 - ?
dc.language ENG
dc.language.iso en_US en_US
dc.relation.ispartof BMC Med Genet
dc.relation.isversionof 10.1186/1471-2350-11-9
dc.subject Adult
dc.subject Aged
dc.subject Alleles
dc.subject Alternative Splicing
dc.subject Cholesterol, HDL
dc.subject Cohort Studies
dc.subject Estrogens
dc.subject Female
dc.subject Genotype
dc.subject Haplotypes
dc.subject Humans
dc.subject Lipids
dc.subject Liver
dc.subject Male
dc.subject Middle Aged
dc.subject Polymorphism, Single Nucleotide
dc.subject Postmenopause
dc.subject Protein Isoforms
dc.subject Scavenger Receptors, Class B
dc.subject Sex Factors
dc.subject Triglycerides
dc.title Impact of gene variants on sex-specific regulation of human Scavenger receptor class B type 1 (SR-BI) expression in liver and association with lipid levels in a population-based study.
dc.title.alternative en_US
dc.type Journal Article
dc.description.version Version of Record en_US 2010-1-19 en_US
duke.description.endpage 9 en_US
duke.description.issue en_US
duke.description.startpage 9 en_US
duke.description.volume 11 en_US
dc.relation.journal Bmc Medical Genetics en_US
pubs.organisational-group /Duke
pubs.organisational-group /Duke/Pratt School of Engineering
pubs.organisational-group /Duke/Pratt School of Engineering/Biomedical Engineering
pubs.organisational-group /Duke/School of Medicine
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Community and Family Medicine
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Medicine
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Medicine/Medicine, Cardiology
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Medicine/Medicine, Endocrinology, Metabolism, and Nutrition
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Neurology
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Neurology/Neurology, Behavioral Neurology
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Pathology
pubs.organisational-group /Duke/School of Medicine/Institutes and Centers
pubs.organisational-group /Duke/School of Medicine/Institutes and Centers/Duke Cancer Institute
pubs.organisational-group /Duke/School of Nursing
pubs.organisational-group /Duke/School of Nursing/School of Nursing
pubs.publication-status Published online
pubs.volume 11
dc.identifier.eissn 1471-2350

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