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Title:Independent and interacting effects of diet and genetic risk on obesity-related comorbidities
Author(s):Hannon, Bridget Ann
Director of Research:Teran-Garcia, Margarita; Khan, Naiman A
Doctoral Committee Chair(s):Donovan, Sharon M
Doctoral Committee Member(s):Holscher, Hannah D; Nakamura, Manabu T; Rowitz, Blair M
Department / Program:Nutritional Sciences
Discipline:Nutritional Sciences
Degree Granting Institution:University of Illinois at Urbana-Champaign
Degree:Ph.D.
Genre:Dissertation
Subject(s):Dyslipidemia, nutrigenetics, dietary fat
Abstract:Introduction: Dyslipidemia results from behavioral and biological factors. Elevated triglyceride (TG) and decreased high-density lipoprotein cholesterol (HDL-C) concentrations are common in obesity. Dietary guidelines for dyslipidemia management encourage replacing saturated (SFA) with unsaturated fat (UFA) and increasing fiber intake. Diet alone does not produce metabolic disease, and genetic variation can increase dyslipidemia risk. Nutrigenetics is a body of research investigating dietary and genetic interactions, but less research exists in non-European populations and individuals with obesity. Our objective was to explore dietary and genetic factors associated with dyslipidemia in populations at risk for metabolic disease. Methods: Meta-analysis of randomized controlled trials (RCT) was conducted investigating SFA-UFA replacement on total cholesterol (TC), HDL-C, and TG concentrations. Genetic contributions to dyslipidemia in Mexicans were explored through creation of a genetic risk score (GRS) from SNPs associated with dyslipidemia. Nutrigenetic interactions were explored in adults with obesity enrolled in a clinical trial, who were randomized to receive a meal with or without an avocado for 12 weeks. Interactions among dietary fat intake, genotype, and blood lipid concentrations were determined pre- and post-intervention. Results: In a meta-analysis of 8 RCT, SFA-UFA replacement on TC concentrations approached significance (P=0.06) in favor of UFA intake. GRS was significantly associated with TG and HDL-C. Among adults enrolled in the clinical trial, dietary fat intake and genotype interactively impacted TC and HDL-C concentrations at baseline. Following dietary intervention, several gene-diet interactions were associated with changes in TC and HDL-C. The glucokinase regulator rs1260326 SNP was associated with TC changes, by which individuals in the avocado group experienced differential changes by presence or absence of the risk allele. Conclusions: SFA-UFA replacement may not be effective in adults with obesity, yet remains a key recommendation in dietary guidelines. Cumulative genetic risk affects HDL-C and TG in the Mexican population, who experience increased dyslipidemia prevalence but remain underrepresented in genetic research. Nutrigenetic interactions between lipid-metabolism related SNPs and dietary fat intake were associated with blood lipid concentrations at baseline and following dietary fat modification. Exploring gene-diet interactions may provide insight into treatment response variability and the development of dyslipidemia despite behavioral risk.
Issue Date:2020-04-22
Type:Thesis
URI:http://hdl.handle.net/2142/108113
Rights Information:© 2020 Bridget Ann Hannon
Date Available in IDEALS:2020-08-26
Date Deposited:2020-05


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