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Investigating the role of sex and genetic variation in the FADS1/2 genes on lipid and fatty acid profiles and the potential impact on response to EPA and DHA supplementation

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Title: Investigating the role of sex and genetic variation in the FADS1/2 genes on lipid and fatty acid profiles and the potential impact on response to EPA and DHA supplementation
Author: Klingel, Shannon
Department: Department of Human Health and Nutritional Sciences
Program: Human Health and Nutritional Sciences
Advisor: Mutch, David
Abstract: Cardiovascular disease (CVD) is the number one cause of death globally, with well-established risk factors and biomarkers. This thesis aimed to understand whether genetic variants and biological sex impact CVD risk factors and if they modify an individual’s response to treatment with the omega-3 polyunsaturated fatty acids (n-3 PUFA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). In Study 1, it was found that sex differences in blood lipid and fatty acid (FA) levels in humans are not associated with variants in lipid metabolism genes, including the rs174537 single nucleotide polymorphism (SNP) in fatty acid desaturase 1 (FADS1). However, as a whole, major alleles for this SNP had higher circulating levels of arachidonic acid (AA) and lower dihomo-gamma-linoleic acid (DGLA). Given that the FADS1 genotype was found to influence circulating FA profiles in a sex-independent manner, we next hypothesized that this same SNP may also influence FA profiles in adipose tissue. Thus, in Study 2, it was demonstrated that FADS1 genotype is associated with different subcutaneous adipose tissue (SAT) FA profiles. Specifically, SAT levels of AA and DGLA explain ~19% of the variance between genotype. As both Study 1 and 2 were static and assessed the impact of genetic variance and sex on CVD risk factors, Study 3 investigated if these same factors influence response to n-3 FA treatment. Using a randomized double-blind placebo-controlled study, the independent effects of 12 weeks of treatment with EPA or DHA on blood lipid and FA levels was examined in healthy men and women. Results showed that DHA treatment reduced circulating triglyceride (TAG) levels, while EPA did not. This effect was more efficacious in individuals with higher TAG levels at baseline but was not dependent on biological sex or FADS1 genotype. In totality, this thesis provides further understanding of the role that genetic variance and sex have in the regulation of blood FA, blood lipids, and adipose tissue FA, while also adding novel insights into how these factors influence an individual’s response to n-3 PUFA treatment.
URI: http://hdl.handle.net/10214/17612
Date: 2019-11
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