title: Vascular Disease Is Associated With the Expression of Genes for Intestinal Cholesterol Transport and Metabolism.
abstract: Intestinal cholesterol metabolism is important in influencing postprandial lipoprotein concentrations, and might be important in the development of vascular disease.
  
  
  
  This study evaluated associations between expression of intestinal cholesterol metabolism genes, postprandial lipid metabolism, and endothelial function/early vascular disease in human subjects.
  
  
  
  One hundred patients undergoing routine oesophago-gastro-duodenoscopy were recruited. mRNA levels of Nieman-Pick C1-like 1 protein (NPC1L1), ABC-G5, ABC-G8, ABC-A1, microsomal tissue transport protein (MTTP), and sterol-regulatory element-binding protein (SREBP)-2 were measured in duodenal biopsies using quantitative reverse transcription polymerase chain reaction. Postprandially, serum lipid and glycemic profiles were measured, endothelial function was assessed using fasting, and postprandial flow-mediated dilatation (FMD) and carotid intima-media thickness (IMT). Subjects were divided into those above and below the median value of relative expression of each gene, and results were compared between the groups.
  
  
  
  There were no between-group differences in demographic variables or classical cardiovascular risks. For all genes, the postprandial triglyceride incremental area under the curve was greater (P < 0.05) in the group with greater expression. Postprandial apolipoprotein B48 (ApoB48) levels were greater (P < 0.05) in groups with greater expression of NPC1L1, ABC-G8, and SREBP-2. For all genes, postprandial but not fasting FMD was lower (P < 0.01) in the group with greater expression. Triglyceride and ApoB48 levels correlated significantly with postprandial FMD. Carotid artery IMT was greater (P < 0.05) in groups with greater expression of MTTP, ABC-A1, and SREBP-2.
  
  
  
  Intestinal cholesterol metabolism gene expression is significantly associated with postprandial increment in triglycerides, intestinal ApoB48, and reduced postprandial FMD. Some genes were also associated with increased IMT. These findings suggest a role of intestinal cholesterol metabolism in development of early vascular disease.
authors.affiliation: Department of Endocrinology and Diabetes Mellitus and.
authors.forename: William M
authors.initials: WM
authors.lastname: Widdowson
authors.affiliation: Department of Endocrinology and Diabetes Mellitus and.
authors.forename: Anne
authors.initials: A
authors.lastname: McGowan
authors.affiliation: Department of Surgery, St. James's Hospital, Dublin 8, Ireland.
authors.forename: James
authors.initials: J
authors.lastname: Phelan
authors.affiliation: Department of Chemical Pathology, Tallaght Hospital, Tallaght, Dublin 24, Ireland; and.
authors.forename: Gerard
authors.initials: G
authors.lastname: Boran
authors.affiliation: Department of Surgery, St. James's Hospital, Dublin 8, Ireland.
authors.forename: John
authors.initials: J
authors.lastname: Reynolds
authors.affiliation: Department of Endocrinology and Diabetes Mellitus and.
authors.forename: James
authors.initials: J
authors.lastname: Gibney
mesh_terms: D001692:Biological Transport; D015415:Biomarkers / Q000378:metabolism*; D059168:Carotid Intima-Media Thickness; D002784:Cholesterol / Q000235:genetics / Q000378:metabolism*; D016145:Endoscopy, Digestive System; D005215:Fasting / Q000502:physiology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period; D011379:Prognosis; D014652:Vascular Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*
chemical_list: D015415:Biomarkers; D002784:Cholesterol