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Sex-specific effects of scavenger receptor class B type 1 (SR-BI) gene variants on serum lipid levels and hepatic gene expression.

Publication ,  Journal Article
Chiba Falek, O; Nichols, M; Suchindran, S; Guyton, JR; Ginsburg, GS; Barrett Connor, E; McCarthy, JJ
Published in: BMC medical genetics
January 2010

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=9.2 x 10-4) and triglycerides (p=1.3 x 10-3) and the triglyceride:HDL cholesterol ratio (p=2.7 x 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

Duke Scholars

Published In

BMC medical genetics

ISSN

1471-2350

Publication Date

January 2010

Volume

11

Issue

1

Start / End Page

9

Related Subject Headings

  • Genetics & Heredity
  • 1103 Clinical Sciences
  • 0604 Genetics
 

Citation

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Chiba Falek, O., Nichols, M., Suchindran, S., Guyton, J. R., Ginsburg, G. S., Barrett Connor, E., & McCarthy, J. J. (2010). Sex-specific effects of scavenger receptor class B type 1 (SR-BI) gene variants on serum lipid levels and hepatic gene expression. BMC Medical Genetics, 11(1), 9.
Chiba Falek, O., M. Nichols, S. Suchindran, J. R. Guyton, G. S. Ginsburg, E. Barrett Connor, and J. J. McCarthy. “Sex-specific effects of scavenger receptor class B type 1 (SR-BI) gene variants on serum lipid levels and hepatic gene expression.BMC Medical Genetics 11, no. 1 (January 2010): 9.
Chiba Falek O, Nichols M, Suchindran S, Guyton JR, Ginsburg GS, Barrett Connor E, et al. Sex-specific effects of scavenger receptor class B type 1 (SR-BI) gene variants on serum lipid levels and hepatic gene expression. BMC medical genetics. 2010 Jan;11(1):9.
Chiba Falek O, Nichols M, Suchindran S, Guyton JR, Ginsburg GS, Barrett Connor E, McCarthy JJ. Sex-specific effects of scavenger receptor class B type 1 (SR-BI) gene variants on serum lipid levels and hepatic gene expression. BMC medical genetics. 2010 Jan;11(1):9.
Journal cover image

Published In

BMC medical genetics

ISSN

1471-2350

Publication Date

January 2010

Volume

11

Issue

1

Start / End Page

9

Related Subject Headings

  • Genetics & Heredity
  • 1103 Clinical Sciences
  • 0604 Genetics