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

BMC Medical Genetics

Research Article

Elizabeth Barrett-Connor¹  John Guyton²  Marshall Nichols³  Ornit Chiba-Falek³  Geoffrey S Ginsburg³  Jeanette J McCarthy³  Sunil Suchindran³ 

[1] Department of Family and Preventive Medicine, University of California at San Diego, 92121, San Diego, CA, USA;Division of Endocrinology, Duke University Medical Center, 27710, Durham, NC, USA;Institute for Genome Sciences and Policy, Duke University Medical Center, 27710, Durham, NC, USA;

关键词: High Density Lipoprotein Cholesterol;    Haplotype Block;    Serum Lipid Level;    High Density Lipoprotein Cholesterol Level;    Splice Form;   

DOI  :  10.1186/1471-2350-11-9

 received in 2009-07-13, accepted in 2010-01-19,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundSeveral 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.MethodsWe 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.ResultsSeveral 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 = 9.2 × 10-4) and triglycerides (p = 1.3 × 10-3) and the triglyceride:HDL cholesterol ratio (p = 2.7 × 10-4). 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).ConclusionsEstrogen 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.

【 授权许可】

Unknown   
© Chiba-Falek et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.