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Diet-gene interactions and PUFA metabolism: a potential contributor to health disparities and human diseases.

Chilton FH, Murphy RC, Wilson BA, Sergeant S, Ainsworth H, Seeds MC, Mathias RA - Nutrients (2014)

Bottom Line: Recent studies have uncovered population-related genetic variation in the LCPUFA biosynthetic pathway (especially within the fatty acid desaturase gene (FADS) cluster) that is associated with levels of circulating and tissue PUFAs and several biomarkers and clinical endpoints of cardiovascular disease (CVD).Importantly, populations of African descent have higher frequencies of variants associated with elevated levels of arachidonic acid (ARA), CVD biomarkers and disease endpoints.These observations raise important questions of whether gene-PUFA interactions are differentially driving the risk of cardiovascular and other diseases in diverse populations, and contributing to health disparities, especially in African American populations.

View Article: PubMed Central - PubMed

Affiliation: The Center for Botanical Lipids and Inflammatory Disease Prevention, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA. schilton@wakehealth.edu.

ABSTRACT
The "modern western" diet (MWD) has increased the onset and progression of chronic human diseases as qualitatively and quantitatively maladaptive dietary components give rise to obesity and destructive gene-diet interactions. There has been a three-fold increase in dietary levels of the omega-6 (n-6) 18 carbon (C18), polyunsaturated fatty acid (PUFA) linoleic acid (LA; 18:2n-6), with the addition of cooking oils and processed foods to the MWD. Intense debate has emerged regarding the impact of this increase on human health. Recent studies have uncovered population-related genetic variation in the LCPUFA biosynthetic pathway (especially within the fatty acid desaturase gene (FADS) cluster) that is associated with levels of circulating and tissue PUFAs and several biomarkers and clinical endpoints of cardiovascular disease (CVD). Importantly, populations of African descent have higher frequencies of variants associated with elevated levels of arachidonic acid (ARA), CVD biomarkers and disease endpoints. Additionally, nutrigenomic interactions between dietary n-6 PUFAs and variants in genes that encode for enzymes that mobilize and metabolize ARA to eicosanoids have been identified. These observations raise important questions of whether gene-PUFA interactions are differentially driving the risk of cardiovascular and other diseases in diverse populations, and contributing to health disparities, especially in African American populations.

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Related in: MedlinePlus

Associations between FADS1 variants and intermediate, molecular phenotypes (IPs), such as metabolic traits. This figure illustrates that the strength of an association is related to the molecular step(s) and metabolite(s) most impacted by genetic variants. In this case, FADS1 variants are most strongly associated with the conversion DGLA to ARA, and thus there are strong associations between the ratio of ARA-containing phospholipids to DGLA-containing phospholipids. This in turn impacts levels of circulating and cellular phospholipid, but the association with FADS1 variants is not as strong because more molecular steps are involved. Levels of phospholipids in turn affects cholesterol levels in lipoprotein particles (as phospholipids and cholesterol esters within lipoprotein particles contain PUFAs) but again the associations are weaker due to the numerous factors (FADS1 variants being only one) that effect total cholesterol levels. Adapted from Gieger et al. [98]
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nutrients-06-01993-f003: Associations between FADS1 variants and intermediate, molecular phenotypes (IPs), such as metabolic traits. This figure illustrates that the strength of an association is related to the molecular step(s) and metabolite(s) most impacted by genetic variants. In this case, FADS1 variants are most strongly associated with the conversion DGLA to ARA, and thus there are strong associations between the ratio of ARA-containing phospholipids to DGLA-containing phospholipids. This in turn impacts levels of circulating and cellular phospholipid, but the association with FADS1 variants is not as strong because more molecular steps are involved. Levels of phospholipids in turn affects cholesterol levels in lipoprotein particles (as phospholipids and cholesterol esters within lipoprotein particles contain PUFAs) but again the associations are weaker due to the numerous factors (FADS1 variants being only one) that effect total cholesterol levels. Adapted from Gieger et al. [98]

Mentions: Three members of the fatty acid desaturase (FADS) gene family on chromosome 11q12–13 [95,96] include FADS1 and FADS2, demonstrated to code for the enzymes, Δ5 and Δ6 desaturase activities, respectively, while less is known about FADS3. Over the past decade, genome-wide association studies (GWAS) have identified a number of genetic polymorphisms that convey increased risk for coronary artery disease, diabetes, cancer, and other common diseases. Recent studies have combined GWAS analysis with the emerging area of metabolomics to more directly address intermediate molecular phenotypes (IP) involved in human diseases (Figure 3).


Diet-gene interactions and PUFA metabolism: a potential contributor to health disparities and human diseases.

Chilton FH, Murphy RC, Wilson BA, Sergeant S, Ainsworth H, Seeds MC, Mathias RA - Nutrients (2014)

Associations between FADS1 variants and intermediate, molecular phenotypes (IPs), such as metabolic traits. This figure illustrates that the strength of an association is related to the molecular step(s) and metabolite(s) most impacted by genetic variants. In this case, FADS1 variants are most strongly associated with the conversion DGLA to ARA, and thus there are strong associations between the ratio of ARA-containing phospholipids to DGLA-containing phospholipids. This in turn impacts levels of circulating and cellular phospholipid, but the association with FADS1 variants is not as strong because more molecular steps are involved. Levels of phospholipids in turn affects cholesterol levels in lipoprotein particles (as phospholipids and cholesterol esters within lipoprotein particles contain PUFAs) but again the associations are weaker due to the numerous factors (FADS1 variants being only one) that effect total cholesterol levels. Adapted from Gieger et al. [98]
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4042578&req=5

nutrients-06-01993-f003: Associations between FADS1 variants and intermediate, molecular phenotypes (IPs), such as metabolic traits. This figure illustrates that the strength of an association is related to the molecular step(s) and metabolite(s) most impacted by genetic variants. In this case, FADS1 variants are most strongly associated with the conversion DGLA to ARA, and thus there are strong associations between the ratio of ARA-containing phospholipids to DGLA-containing phospholipids. This in turn impacts levels of circulating and cellular phospholipid, but the association with FADS1 variants is not as strong because more molecular steps are involved. Levels of phospholipids in turn affects cholesterol levels in lipoprotein particles (as phospholipids and cholesterol esters within lipoprotein particles contain PUFAs) but again the associations are weaker due to the numerous factors (FADS1 variants being only one) that effect total cholesterol levels. Adapted from Gieger et al. [98]
Mentions: Three members of the fatty acid desaturase (FADS) gene family on chromosome 11q12–13 [95,96] include FADS1 and FADS2, demonstrated to code for the enzymes, Δ5 and Δ6 desaturase activities, respectively, while less is known about FADS3. Over the past decade, genome-wide association studies (GWAS) have identified a number of genetic polymorphisms that convey increased risk for coronary artery disease, diabetes, cancer, and other common diseases. Recent studies have combined GWAS analysis with the emerging area of metabolomics to more directly address intermediate molecular phenotypes (IP) involved in human diseases (Figure 3).

Bottom Line: Recent studies have uncovered population-related genetic variation in the LCPUFA biosynthetic pathway (especially within the fatty acid desaturase gene (FADS) cluster) that is associated with levels of circulating and tissue PUFAs and several biomarkers and clinical endpoints of cardiovascular disease (CVD).Importantly, populations of African descent have higher frequencies of variants associated with elevated levels of arachidonic acid (ARA), CVD biomarkers and disease endpoints.These observations raise important questions of whether gene-PUFA interactions are differentially driving the risk of cardiovascular and other diseases in diverse populations, and contributing to health disparities, especially in African American populations.

View Article: PubMed Central - PubMed

Affiliation: The Center for Botanical Lipids and Inflammatory Disease Prevention, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA. schilton@wakehealth.edu.

ABSTRACT
The "modern western" diet (MWD) has increased the onset and progression of chronic human diseases as qualitatively and quantitatively maladaptive dietary components give rise to obesity and destructive gene-diet interactions. There has been a three-fold increase in dietary levels of the omega-6 (n-6) 18 carbon (C18), polyunsaturated fatty acid (PUFA) linoleic acid (LA; 18:2n-6), with the addition of cooking oils and processed foods to the MWD. Intense debate has emerged regarding the impact of this increase on human health. Recent studies have uncovered population-related genetic variation in the LCPUFA biosynthetic pathway (especially within the fatty acid desaturase gene (FADS) cluster) that is associated with levels of circulating and tissue PUFAs and several biomarkers and clinical endpoints of cardiovascular disease (CVD). Importantly, populations of African descent have higher frequencies of variants associated with elevated levels of arachidonic acid (ARA), CVD biomarkers and disease endpoints. Additionally, nutrigenomic interactions between dietary n-6 PUFAs and variants in genes that encode for enzymes that mobilize and metabolize ARA to eicosanoids have been identified. These observations raise important questions of whether gene-PUFA interactions are differentially driving the risk of cardiovascular and other diseases in diverse populations, and contributing to health disparities, especially in African American populations.

Show MeSH
Related in: MedlinePlus