The ABCG8 G574R variant, serum plant sterol levels, and cardiovascular disease risk in the old order amish

Richard B. Horenstein, Braxton D. Mitchell, Wendy S. Post, Dieter Lütjohann, Klaus Von Bergmann, Kathleen A. Ryan, Michael Terrin, Alan R. Shuldiner, Nanette I. Steinle

Research output: Contribution to journalArticle

Abstract

Objective-: To determine whether long-term exposure to moderate elevations in plasma plant sterol levels increases risk for atherosclerosis. METHODS AND RESULTS-: In Old Order Amish participants aged 18 to 85 years, with (n=110) and without (n=181) 1 copy of the ABCG8 G574R variant, we compared mean plasma levels of plant sterols and cholesterol precursors and carotid intima-media wall thickness. Carriers of a single 574R allele had increased plant sterol levels (eg, 35%-37% higher plasma levels of sitosterol, campesterol, and stigmasterol) and increased plant sterol/cholesterol ratios (P<0.001 for all). 574R carriers had significantly decreased levels of lathosterol and lanosterol, precursors in a pathway for endogenous cholesterol synthesis, suggesting that plant sterols may alter regulation of genes involved in cholesterol synthesis. The G574R variant was not associated with high-density lipoprotein cholesterol or low-density lipoprotein cholesterol levels. Compared with noncarriers, 574R carriers had decreased carotid intima-media wall thickness (0.62 versus 0.66 mm; age-and sex-adjusted P=0.03). Adjustment for body weight, blood pressure, and standard lipid measures (high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides) did not alter this association. CONCLUSION-: Although the G574R variant is associated with moderately elevated plant sterol levels, carriers of the 574R allele had modestly lower levels of carotid wall thickness compared with noncarriers.

Original languageEnglish (US)
Pages (from-to)413-419
Number of pages7
JournalArteriosclerosis, thrombosis, and vascular biology
Volume33
Issue number2
DOIs
StatePublished - Feb 2013

Keywords

  • ABC transporter
  • atherosclerosis
  • lipids
  • plant sterols
  • sitosterol

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'The ABCG8 G574R variant, serum plant sterol levels, and cardiovascular disease risk in the old order amish'. Together they form a unique fingerprint.

  • Cite this

    Horenstein, R. B., Mitchell, B. D., Post, W. S., Lütjohann, D., Von Bergmann, K., Ryan, K. A., Terrin, M., Shuldiner, A. R., & Steinle, N. I. (2013). The ABCG8 G574R variant, serum plant sterol levels, and cardiovascular disease risk in the old order amish. Arteriosclerosis, thrombosis, and vascular biology, 33(2), 413-419. https://doi.org/10.1161/ATVBAHA.112.245480