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The impact of FADS genetic variants on ω6 polyunsaturated fatty acid metabolism in African Americans.

Mathias RA, Sergeant S, Ruczinski I, Torgerson DG, Hugenschmidt CE, Kubala M, Vaidya D, Suktitipat B, Ziegler JT, Ivester P, Case D, Yanek LR, Freedman BI, Rudock ME, Barnes KC, Langefeld CD, Becker LC, Bowden DW, Becker DM, Chilton FH - BMC Genet. (2011)

Bottom Line: Ancestry-related differences were observed at an upstream marker previously associated with AA levels (rs174537), wherein, 79-82% of African Americans carry two copies of the G allele compared to only 42-45% of European Americans.Importantly, the allelic effect of the G allele, which is associated with enhanced conversion of DGLA to AA, on enzymatic efficiency was similar in both groups.We conclude that the impact of FADS genetic variants on PUFA metabolism, specifically AA levels, is likely more pronounced in African Americans due to the larger proportion of individuals carrying the genotype associated with increased FADS1 enzymatic conversion of DGLA to AA.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of General Internal Medicine, Department of Medicine, The GeneSTAR Research Program, The Johns Hopkins University, Baltimore, MD 21224, USA. rmathias@jhmi.edu

ABSTRACT

Background: Arachidonic acid (AA) is a long-chain omega-6 polyunsaturated fatty acid (PUFA) synthesized from the precursor dihomo-gamma-linolenic acid (DGLA) that plays a vital role in immunity and inflammation. Variants in the Fatty Acid Desaturase (FADS) family of genes on chromosome 11q have been shown to play a role in PUFA metabolism in populations of European and Asian ancestry; no work has been done in populations of African ancestry to date.

Results: In this study, we report that African Americans have significantly higher circulating levels of plasma AA (p = 1.35 × 10(-48)) and lower DGLA levels (p = 9.80 × 10(-11)) than European Americans. Tests for association in N = 329 individuals across 80 nucleotide polymorphisms (SNPs) in the Fatty Acid Desaturase (FADS) locus revealed significant association with AA, DGLA and the AA/DGLA ratio, a measure of enzymatic efficiency, in both racial groups (peak signal p = 2.85 × 10(-16) in African Americans, 2.68 × 10(-23) in European Americans). Ancestry-related differences were observed at an upstream marker previously associated with AA levels (rs174537), wherein, 79-82% of African Americans carry two copies of the G allele compared to only 42-45% of European Americans. Importantly, the allelic effect of the G allele, which is associated with enhanced conversion of DGLA to AA, on enzymatic efficiency was similar in both groups.

Conclusions: We conclude that the impact of FADS genetic variants on PUFA metabolism, specifically AA levels, is likely more pronounced in African Americans due to the larger proportion of individuals carrying the genotype associated with increased FADS1 enzymatic conversion of DGLA to AA.

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Population-based Differences in Plasma Fatty Acid Concentrations. Trait distribution differences between African American (N = 174) and European American (N = 155) individuals from the GeneSTAR study showing distributions in age- and gender-adjusted ω6 PUFAs (LA, GLA, DGLA and AA) and FADS1 enzymatic efficiency (AA/DGLA). Each sample is represented by a single dot in blue for African Americans and red for European Americans. Sample means and confidence interval for the sample mean are presented as the horizontal black line and surrounding green box, respectively. Genes known to play a pivotal role in the desaturation and elongation step in the metabolism of AA are illustrated. Individual PUFAs were expressed as percent of total fatty acids in a sample, and the ratio of AA mass/DGLA mass was calculated as a measure of FADS1 enzymatic efficiency.
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Figure 1: Population-based Differences in Plasma Fatty Acid Concentrations. Trait distribution differences between African American (N = 174) and European American (N = 155) individuals from the GeneSTAR study showing distributions in age- and gender-adjusted ω6 PUFAs (LA, GLA, DGLA and AA) and FADS1 enzymatic efficiency (AA/DGLA). Each sample is represented by a single dot in blue for African Americans and red for European Americans. Sample means and confidence interval for the sample mean are presented as the horizontal black line and surrounding green box, respectively. Genes known to play a pivotal role in the desaturation and elongation step in the metabolism of AA are illustrated. Individual PUFAs were expressed as percent of total fatty acids in a sample, and the ratio of AA mass/DGLA mass was calculated as a measure of FADS1 enzymatic efficiency.

Mentions: Figure 1 shows the distribution of ω-6 PUFAs in the African American and European American adults from the GeneSTAR study. With the exception of DGLA, ω-6 PUFAs examined all appeared to be significantly higher in the African Americans compared to European Americans. There was an increase in the magnitude of the difference between the two racial groups as the length of the carbon chain of the PUFAs increased (p-value for LA = 0.001, for GLA = 1.37 × 10-06, for DGLA = 9.80 × 10-11 and for AA = 1.35 × 10-48). Furthermore, the ratio of FADS1 product to precursor (AA/DGLA) was markedly higher in the African American subjects (p = 2.06 × 10-38) suggesting a differential ability to convert DGLA to AA through FADS1 pathway between the two groups.


The impact of FADS genetic variants on ω6 polyunsaturated fatty acid metabolism in African Americans.

Mathias RA, Sergeant S, Ruczinski I, Torgerson DG, Hugenschmidt CE, Kubala M, Vaidya D, Suktitipat B, Ziegler JT, Ivester P, Case D, Yanek LR, Freedman BI, Rudock ME, Barnes KC, Langefeld CD, Becker LC, Bowden DW, Becker DM, Chilton FH - BMC Genet. (2011)

Population-based Differences in Plasma Fatty Acid Concentrations. Trait distribution differences between African American (N = 174) and European American (N = 155) individuals from the GeneSTAR study showing distributions in age- and gender-adjusted ω6 PUFAs (LA, GLA, DGLA and AA) and FADS1 enzymatic efficiency (AA/DGLA). Each sample is represented by a single dot in blue for African Americans and red for European Americans. Sample means and confidence interval for the sample mean are presented as the horizontal black line and surrounding green box, respectively. Genes known to play a pivotal role in the desaturation and elongation step in the metabolism of AA are illustrated. Individual PUFAs were expressed as percent of total fatty acids in a sample, and the ratio of AA mass/DGLA mass was calculated as a measure of FADS1 enzymatic efficiency.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3118962&req=5

Figure 1: Population-based Differences in Plasma Fatty Acid Concentrations. Trait distribution differences between African American (N = 174) and European American (N = 155) individuals from the GeneSTAR study showing distributions in age- and gender-adjusted ω6 PUFAs (LA, GLA, DGLA and AA) and FADS1 enzymatic efficiency (AA/DGLA). Each sample is represented by a single dot in blue for African Americans and red for European Americans. Sample means and confidence interval for the sample mean are presented as the horizontal black line and surrounding green box, respectively. Genes known to play a pivotal role in the desaturation and elongation step in the metabolism of AA are illustrated. Individual PUFAs were expressed as percent of total fatty acids in a sample, and the ratio of AA mass/DGLA mass was calculated as a measure of FADS1 enzymatic efficiency.
Mentions: Figure 1 shows the distribution of ω-6 PUFAs in the African American and European American adults from the GeneSTAR study. With the exception of DGLA, ω-6 PUFAs examined all appeared to be significantly higher in the African Americans compared to European Americans. There was an increase in the magnitude of the difference between the two racial groups as the length of the carbon chain of the PUFAs increased (p-value for LA = 0.001, for GLA = 1.37 × 10-06, for DGLA = 9.80 × 10-11 and for AA = 1.35 × 10-48). Furthermore, the ratio of FADS1 product to precursor (AA/DGLA) was markedly higher in the African American subjects (p = 2.06 × 10-38) suggesting a differential ability to convert DGLA to AA through FADS1 pathway between the two groups.

Bottom Line: Ancestry-related differences were observed at an upstream marker previously associated with AA levels (rs174537), wherein, 79-82% of African Americans carry two copies of the G allele compared to only 42-45% of European Americans.Importantly, the allelic effect of the G allele, which is associated with enhanced conversion of DGLA to AA, on enzymatic efficiency was similar in both groups.We conclude that the impact of FADS genetic variants on PUFA metabolism, specifically AA levels, is likely more pronounced in African Americans due to the larger proportion of individuals carrying the genotype associated with increased FADS1 enzymatic conversion of DGLA to AA.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of General Internal Medicine, Department of Medicine, The GeneSTAR Research Program, The Johns Hopkins University, Baltimore, MD 21224, USA. rmathias@jhmi.edu

ABSTRACT

Background: Arachidonic acid (AA) is a long-chain omega-6 polyunsaturated fatty acid (PUFA) synthesized from the precursor dihomo-gamma-linolenic acid (DGLA) that plays a vital role in immunity and inflammation. Variants in the Fatty Acid Desaturase (FADS) family of genes on chromosome 11q have been shown to play a role in PUFA metabolism in populations of European and Asian ancestry; no work has been done in populations of African ancestry to date.

Results: In this study, we report that African Americans have significantly higher circulating levels of plasma AA (p = 1.35 × 10(-48)) and lower DGLA levels (p = 9.80 × 10(-11)) than European Americans. Tests for association in N = 329 individuals across 80 nucleotide polymorphisms (SNPs) in the Fatty Acid Desaturase (FADS) locus revealed significant association with AA, DGLA and the AA/DGLA ratio, a measure of enzymatic efficiency, in both racial groups (peak signal p = 2.85 × 10(-16) in African Americans, 2.68 × 10(-23) in European Americans). Ancestry-related differences were observed at an upstream marker previously associated with AA levels (rs174537), wherein, 79-82% of African Americans carry two copies of the G allele compared to only 42-45% of European Americans. Importantly, the allelic effect of the G allele, which is associated with enhanced conversion of DGLA to AA, on enzymatic efficiency was similar in both groups.

Conclusions: We conclude that the impact of FADS genetic variants on PUFA metabolism, specifically AA levels, is likely more pronounced in African Americans due to the larger proportion of individuals carrying the genotype associated with increased FADS1 enzymatic conversion of DGLA to AA.

Show MeSH
Related in: MedlinePlus