title: The ABCG8 G574R variant, serum plant sterol levels, and cardiovascular disease risk in the Old Order Amish.
abstract: OBJECTIVE
  To determine whether long-term exposure to moderate elevations in plasma plant sterol levels increases risk for atherosclerosis.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, MD 21201, USA. rhorenst@medicine.umaryland.edu
authors.forename: Richard B
authors.initials: RB
authors.lastname: Horenstein
authors.forename: Braxton D
authors.initials: BD
authors.lastname: Mitchell
authors.forename: Wendy S
authors.initials: WS
authors.lastname: Post
authors.forename: Dieter
authors.initials: D
authors.lastname: Lütjohann
authors.forename: Klaus
authors.initials: K
authors.lastname: von Bergmann
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Ryan
authors.forename: Michael
authors.initials: M
authors.lastname: Terrin
authors.forename: Alan R
authors.initials: AR
authors.lastname: Shuldiner
authors.forename: Nanette I
authors.initials: NI
authors.lastname: Steinle
mesh_terms: D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061365:Amish / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D002340:Carotid Artery Diseases / Q000097:blood / Q000175:diagnosis / Q000208:ethnology* / Q000235:genetics*; D059168:Carotid Intima-Media Thickness; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000175:diagnosis / Q000208:ethnology* / Q000235:genetics*; D007410:Intestinal Diseases / Q000097:blood / Q000175:diagnosis / Q000208:ethnology* / Q000235:genetics*; D008052:Lipid Metabolism, Inborn Errors / Q000097:blood / Q000175:diagnosis / Q000208:ethnology* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010414:Pennsylvania / Q000453:epidemiology; D010641:Phenotype; D010840:Phytosterols / Q000009:adverse effects / Q000097:blood* / Q000235:genetics; D018570:Risk Assessment; D012307:Risk Factors; D015854:Up-Regulation; D055815:Young Adult
chemical_list: C416946:ABCG8 protein, human; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters; D015415:Biomarkers; D010840:Phytosterols