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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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Dramatic differences in the frequency of derived alleles in a 100 kb region surrounding rs174537 in the Human Genome Diversity Panel Data. (A) is the physical location of the SNPs and genes in the region; (B) is SNP name and the specific derived allele in parenthesis; (C) is the derived allele frequency in orange in 52 populations clustered based on geography; (D) reflects the allele associated with increased LC-PUFA metabolism from published studies.; (E) is the detailed overview of rs174537; (F) shows three distributions within the Tangier Island Population. Adapted from Mathias et al. [149] (Panels A–E) and from Mathias et al [111]. (Panel F).
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nutrients-06-01993-f004: Dramatic differences in the frequency of derived alleles in a 100 kb region surrounding rs174537 in the Human Genome Diversity Panel Data. (A) is the physical location of the SNPs and genes in the region; (B) is SNP name and the specific derived allele in parenthesis; (C) is the derived allele frequency in orange in 52 populations clustered based on geography; (D) reflects the allele associated with increased LC-PUFA metabolism from published studies.; (E) is the detailed overview of rs174537; (F) shows three distributions within the Tangier Island Population. Adapted from Mathias et al. [149] (Panels A–E) and from Mathias et al [111]. (Panel F).

Mentions: This work confirmed marked global differences in the allele frequencies of variants in the FADS gene cluster first noted in our work on African Americans and European Americans, especially at variants strongly associated with the efficiency of conversion of PUFAs. Figure 4 is a detailed synopsis of the patterns of genetic variation in a 100 kb region within the FADS gene cluster and illustrates three points: (1) clearly there are wide differences in the frequencies across numerous SNPs between populations, this is a function of extensive linkage disequilibrium in this region; (2) for SNPs for which allelic effects on LC-PUFA metabolism are known, the specific alleles that favor enhanced LC-PUFA metabolism across populations typically increase with an increasing African admixture component; and (3) rs174537 is notable in that the derived allele is the allele fixed within Africa. It is not clear why the positive selective pressure on the high efficiency FADS variants were lost after the expansion of populations from Africa. We have speculated that once LCPUFAs could be obtained in the diet due to the emergence of hunting, fishing, animal husbandry and other technological advances, the pathway may have lost its selective advantage. In any event, the world is now left with large diverse populations in countries such as the US, which are particularly distinct with regard to the frequency of important FADS cluster variants and potentially their capacity to synthesize n-6 LCPUFAs from very high levels of n-6 C18 PUFAs and particularly LA found in the MWD.


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)

Dramatic differences in the frequency of derived alleles in a 100 kb region surrounding rs174537 in the Human Genome Diversity Panel Data. (A) is the physical location of the SNPs and genes in the region; (B) is SNP name and the specific derived allele in parenthesis; (C) is the derived allele frequency in orange in 52 populations clustered based on geography; (D) reflects the allele associated with increased LC-PUFA metabolism from published studies.; (E) is the detailed overview of rs174537; (F) shows three distributions within the Tangier Island Population. Adapted from Mathias et al. [149] (Panels A–E) and from Mathias et al [111]. (Panel F).
© Copyright Policy
Related In: Results  -  Collection

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

nutrients-06-01993-f004: Dramatic differences in the frequency of derived alleles in a 100 kb region surrounding rs174537 in the Human Genome Diversity Panel Data. (A) is the physical location of the SNPs and genes in the region; (B) is SNP name and the specific derived allele in parenthesis; (C) is the derived allele frequency in orange in 52 populations clustered based on geography; (D) reflects the allele associated with increased LC-PUFA metabolism from published studies.; (E) is the detailed overview of rs174537; (F) shows three distributions within the Tangier Island Population. Adapted from Mathias et al. [149] (Panels A–E) and from Mathias et al [111]. (Panel F).
Mentions: This work confirmed marked global differences in the allele frequencies of variants in the FADS gene cluster first noted in our work on African Americans and European Americans, especially at variants strongly associated with the efficiency of conversion of PUFAs. Figure 4 is a detailed synopsis of the patterns of genetic variation in a 100 kb region within the FADS gene cluster and illustrates three points: (1) clearly there are wide differences in the frequencies across numerous SNPs between populations, this is a function of extensive linkage disequilibrium in this region; (2) for SNPs for which allelic effects on LC-PUFA metabolism are known, the specific alleles that favor enhanced LC-PUFA metabolism across populations typically increase with an increasing African admixture component; and (3) rs174537 is notable in that the derived allele is the allele fixed within Africa. It is not clear why the positive selective pressure on the high efficiency FADS variants were lost after the expansion of populations from Africa. We have speculated that once LCPUFAs could be obtained in the diet due to the emergence of hunting, fishing, animal husbandry and other technological advances, the pathway may have lost its selective advantage. In any event, the world is now left with large diverse populations in countries such as the US, which are particularly distinct with regard to the frequency of important FADS cluster variants and potentially their capacity to synthesize n-6 LCPUFAs from very high levels of n-6 C18 PUFAs and particularly LA found in the MWD.

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