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.

Published online

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Chiba-Falek, O; Nichols, M; Suchindran, S; Guyton, J; Ginsburg, GS; Barrett-Connor, E; McCarthy, JJ

Published Date

  • January 19, 2010

Published In

Volume / Issue

  • 11 /

Start / End Page

  • 9 -

PubMed ID

  • 20085651

Pubmed Central ID

  • 20085651

Electronic International Standard Serial Number (EISSN)

  • 1471-2350

Digital Object Identifier (DOI)

  • 10.1186/1471-2350-11-9

Language

  • eng

Conference Location

  • England