Vascular disease is associated with the expression of genes for intestinal cholesterol transport and metabolism.

Vascular disease is associated with the expression of genes for intestinal cholesterol transport and metabolism.

J Clin Endocrinol Metab. 2016 Nov 14;:jc20162728

Authors: Widdowson WM, McGowan A, Phelan J, Boran G, Reynolds J, Gibney J

Abstract
CONTEXT: Intestinal cholesterol metabolism is important in influencing post-prandial lipoprotein concentrations, and might be important in the development of vascular disease.
OBJECTIVE: This study evaluated associations between expression of intestinal cholesterol metabolism genes, postprandial lipid metabolism, and endothelial function/early vascular disease in human subjects. Design / Patients: One hundred patients undergoing routine oesophago-gastro-duedonscopy were recruited. mRNA levels of NPC1-L1, ABC-G5, ABC-G8, ABC-A1, MTTP, and SREBP-2 were measured in duodenal biopsies using rt-qPCR. Post-prandially, serum lipid and glycaemic profiles were measured, endothelial function was assessed using fasting and post-prandial FMD and carotid IMT was measured using B-mode ultrasonography. Subjects were divided into those above and below the median value of relative expression of each gene and results compared between the groups.
RESULTS: There were no between-group differences in demographic variables or classical cardiovascular risks. For all genes, the postprandial triglyceride incremental AUC was greater (P<0.05) in the group with greater expression. Post-prandial apoB48 levels were greater (P<0.05) in groups with greater expression of NPC1L1, ABC-G8, and SREBP-2. For all genes, post-prandial but not fasting FMD was greater (P<0.01) in the group with greater expression. Triglyceride and ApoB48 levels correlated significantly with postprandial FMD. CIMT was greater (P<0.05) in groups with greater expression of MTTP, ABC-A1, and SREBP-2.
CONCLUSION: Intestinal cholesterol metabolism gene expression is significantly associated with postprandial increment in TG, intestinal Apo B48, and reduced post-prandial FMD. Some genes were also associated with increased IMT. These findings suggest a role of intestinal cholesterol metabolism in development of early vascular disease.

PMID: 27841945 [PubMed - as supplied by publisher]

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