Genetic heterogeneity in the impact of dairy product consumption on cholesterol metabolism in humans

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dc.contributor.authorAbdullah, Mohammad
dc.contributor.examiningcommitteeFriel, James (Human Nutritional Sciences) Eck, Peter (Human Nutritional Sciences) Hatch, Grant (Pharmacology and Therapeutics & Biochemistry and Medical Genetics) Tremblay, Angelo (Laval University)en_US
dc.contributor.supervisorJones, Peter (Human Nutritional Sciences)en_US
dc.date.accessioned2015-12-14T14:09:26Z
dc.date.available2015-12-14T14:09:26Z
dc.date.issued2015-06-27en_US
dc.date.issued2015-01-22en_US
dc.date.issued2014-09-03en_US
dc.degree.disciplineHuman Nutritional Sciencesen_US
dc.degree.levelDoctor of Philosophy (Ph.D.)en_US
dc.description.abstractWith the increased marketing and popularity of a range of dairy products in recent years, research has become widespread concerning the influence of dairy on human health. It is also becoming evident that an individual’s genetic make-up contributes to shaping their health responses to dietary intakes. This research was primarily designed to investigate the impact of genetic variability on responsiveness of cholesterol metabolism, a classic biomarker of cardiovascular health, to the recommended level of dairy consumption in Canada. A secondary objective was to assess the influence of dairy intake on systemic inflammation as an emerging risk factor for cardiovascular disease. In a multicentre, randomized, free-living crossover design, 124 healthy individuals consumed 3 servings/day of conventional low-fat and regular milk, yogurt, and cheese (DAIRY diet) or dairy-free control products (CONTROL diet), each for 28 days as part of a prudent background dietary protocol. At the end of the study, DAIRY was associated with increased plasma concentrations of two established fatty acid biomarkers of dairy fat, pentadecanoic acid (C15:0) and heptadecanoic acid (C17:0), as well as with small increases in serum total cholesterol (TC) and LDL-cholesterol (LDL-C) concentrations. Inter-individual variability in the cholesterol transport gene ABCG5, bile acid synthesis gene CYP7A1, and cholesterol synthesis gene DHCR7 contributed to shaping the degree of TC and LDL-C responsiveness to DAIRY; with higher cholesterol concentrations observed among ABCG5 rs6720173-G/G homozygotes, CYP7A1 rs3808607-G allele carriers, and DHCR7 rs760241-A allele carriers, relative to the C allele, T/T, and G/G carriers of these genes, respectively. Also, after DAIRY, the major allele T homozygosity of CYP7A1 rs3808607 and the minor allele A of DHCR7 rs760241 were associated with reduced plasma [3,4]13C cholesterol enrichment and deuterium incorporation, respectively, suggesting reduced cholesterol absorption and synthesis rates. DAIRY intake did not influence the inflammatory status. Overall, this research has provided evidence of a potential impact of the genomic architecture on responsiveness of cholesterol metabolism to dairy consumption. The novel findings are expected to advance knowledge of the inherited basis by which health biomarkers may be modified in response to whole foods, hence launching an important step towards an era of personalized nutrition.en_US
dc.description.noteFebruary 2016en_US
dc.identifier.citationAMAen_US
dc.identifier.citationVancouveren_US
dc.identifier.citationICMJEen_US
dc.identifier.urihttp://hdl.handle.net/1993/30974
dc.language.isoengen_US
dc.publisherOxford University Pressen_US
dc.publisherCambridge University Pressen_US
dc.publisherAmerican Society for Nutritionen_US
dc.rightsopen accessen_US
dc.subjectDairyen_US
dc.subjectGene-diet interactionen_US
dc.subjectCholesterol metabolismen_US
dc.subjectCardiovascular diseaseen_US
dc.subjectPersonalized nutritionen_US
dc.titleGenetic heterogeneity in the impact of dairy product consumption on cholesterol metabolism in humansen_US
dc.typedoctoral thesisen_US
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