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.contributor.author | Chiba-Falek, Ornit | |
| dc.contributor.author | Nichols, Marshall | |
| dc.contributor.author | Suchindran, Sunil | |
| dc.contributor.author | Guyton, John | |
| dc.contributor.author | Ginsburg, Geoffrey S | |
| dc.contributor.author | Barrett-Connor, Elizabeth | |
| dc.contributor.author | McCarthy, Jeanette J | |
| dc.coverage.spatial | England | |
| dc.date.accessioned | 2011-06-21T17:29:34Z | |
| dc.date.issued | 2010-01-19 | |
| 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.description.version | Version of Record | |
| dc.identifier | ||
| dc.identifier | 1471-2350-11-9 | |
| dc.identifier.eissn | 1471-2350 | |
| dc.identifier.uri | ||
| dc.language | eng | |
| dc.language.iso | en_US | |
| dc.publisher | Springer Science and Business Media LLC | |
| dc.relation.ispartof | BMC Med Genet | |
| dc.relation.isversionof | 10.1186/1471-2350-11-9 | |
| dc.relation.journal | Bmc Medical Genetics | |
| 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 | ||
| dc.type | Journal article | |
| duke.contributor.orcid | Chiba-Falek, Ornit|0000-0002-2529-8785 | |
| duke.contributor.orcid | Ginsburg, Geoffrey S|0000-0003-4739-9808 | |
| duke.date.pubdate | 2010-1-19 | |
| duke.description.issue | ||
| duke.description.volume | 11 | |
| pubs.author-url | ||
| pubs.begin-page | 9 | |
| pubs.organisational-group | Clinical Science Departments | |
| pubs.organisational-group | Community and Family Medicine | |
| pubs.organisational-group | Duke | |
| pubs.organisational-group | Duke Cancer Institute | |
| pubs.organisational-group | Institutes and Centers | |
| pubs.organisational-group | Medicine | |
| pubs.organisational-group | Medicine, Cardiology | |
| pubs.organisational-group | Medicine, Endocrinology, Metabolism, and Nutrition | |
| pubs.organisational-group | Neurology | |
| pubs.organisational-group | Neurology, Behavioral Neurology | |
| pubs.organisational-group | Nursing | |
| pubs.organisational-group | Pathology | |
| pubs.organisational-group | School of Medicine | |
| pubs.organisational-group | School of Nursing | |
| pubs.publication-status | Published online | |
| pubs.volume | 11 |