Intestinal cholesterol-transport gene expression is associated with abnormalities in post-prandial endothelial function and carotid intima-media thickness independent of insulin resistance

W Matthew Widdowson; Anne McGowan; James Phelan; Gerard Boran; John Reynolds; James Gibney

doi:10.1530/endoabs.32.P178

P178

Prev Next

Section Contents Cite

Endocrine Abstracts (2013) 32 P178 | DOI: 10.1530/endoabs.32.P178

ECE2013 Poster Presentations Cardiovascular Endocrinology & Lipid Metabolism (41 abstracts)

Intestinal cholesterol-transport gene expression is associated with abnormalities in post-prandial endothelial function and carotid intima-media thickness independent of insulin resistance

W Matthew Widdowson ¹ , Anne McGowan ¹ , James Phelan ³ , Gerard Boran ² , John Reynolds ³ & James Gibney ¹

Views

Author affiliations

¹Endocrinology Department, Tallaght Hospital, Dublin, Ireland; ²Department of Chemical Pathology, Tallaght Hospital, Dublin, Ireland; ³Department of Surgery, St James’s Hospital, Dublin, Ireland.

Introduction: Intestinal cholesterol absorption is known to be important in post-prandial lipid levels, and implicated in the development of vascular disease. This study evaluated the effect of intestinal gene expression on markers of early vascular disease in a cohort of diabetic and non-diabetic subjects.

Methods: Subjects were identified from routine upper GI lists and enrolled as per local ethics approval. Intestinal gene expression was measured on duodenal biopsy samples, using rtPCR to measure mRNA levels of Niemann-Pick C1-L1, ABCG5, ABCG8, ABCA1, microsomal tissue transport protein (MTTP), and sterol regulatory element-binding protein types 1 and 2. Following a standard mixed meal, serum lipid profiles were measured and insulin resistance was measured via HOMA-IR. Post-prandial endothelial function was assessed via flow-mediated dilatation (FMD) of the brachial artery, and carotid IMT measured using B-mode ultrasonography. Statistical analysis utilised SPSS (Ver 10.1).

Results: One hundred patients were analysed. Intestinal gene expression was associated with alterations in IMT and post-prandial FMD as demonstrated in Table 1, corrected for age, BMI and HOMA-IR.

Fasting and post-prandial lipid levels were not associated with either vascular markers or intestinal gene expression. Gene expression was not affected by smoking status, diabetic staus or gender.

Table 1
	NPC1L1	ABCG5	ABCG8	MTTP	ABCA1	SREBP1	SREBP2
IMT	0.147^a	0.349^†	0.324^†	0.274*	0.229*	0.076^a	0.296^†
PP FMD	−0.245*	−0.197^a	−0.246*	−0.253*	−0.358^†	−0.363^†	−0.287^†
*P<0.05, ^†P<0.01, ^aNS. Values are for R (Pearson’s correlation coefficient).

Conclusion: Intestinal gene expression shows significant association with increased IMT, a marker for early atherosclerotic change, as well as reduced post-prandial FMD, a marker of early endothelial dysfunction. This association appears to be independent of post-prandial lipid levels and glycaemic status.