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

Rasika Mathias, Susan Sergeant, Ingo Ruczinski, Dara G. Torgerson, Christina E. Hugenschmidt, Meghan Kubala, Dhananjay Vaidya, Bhoom Suktitipat, Julie T. Ziegler, Priscilla Ivester, Douglas Case, Lisa Yanek, Barry I. Freedman, Megan E. Rudock, Kathleen C. Barnes, Carl D. Langefeld, Lewis Becker, Donald W. Bowden, Diane M Becker, Floyd H. Chilton

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number50
JournalBMC Genetics
Volume12
DOIs
StatePublished - May 20 2011

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Fatty Acid Desaturases
8,11,14-Eicosatrienoic Acid
Unsaturated Fatty Acids
Arachidonic Acid
African Americans
Omega-6 Fatty Acids
Alleles
Population
Single Nucleotide Polymorphism
Immunity
Nucleotides
Chromosomes
Genotype
Inflammation

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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The impact of FADS genetic variants on ω6 polyunsaturated fatty acid metabolism in African Americans. / Mathias, Rasika; Sergeant, Susan; Ruczinski, Ingo; Torgerson, Dara G.; Hugenschmidt, Christina E.; Kubala, Meghan; Vaidya, Dhananjay; Suktitipat, Bhoom; Ziegler, Julie T.; Ivester, Priscilla; Case, Douglas; Yanek, Lisa; Freedman, Barry I.; Rudock, Megan E.; Barnes, Kathleen C.; Langefeld, Carl D.; Becker, Lewis; Bowden, Donald W.; Becker, Diane M; Chilton, Floyd H.

In: BMC Genetics, Vol. 12, 50, 20.05.2011.

Research output: Contribution to journalArticle

Mathias, R, Sergeant, S, Ruczinski, I, Torgerson, DG, Hugenschmidt, CE, Kubala, M, Vaidya, D, Suktitipat, B, Ziegler, JT, Ivester, P, Case, D, Yanek, L, Freedman, BI, Rudock, ME, Barnes, KC, Langefeld, CD, Becker, L, Bowden, DW, Becker, DM & Chilton, FH 2011, 'The impact of FADS genetic variants on ω6 polyunsaturated fatty acid metabolism in African Americans', BMC Genetics, vol. 12, 50. https://doi.org/10.1186/1471-2156-12-50
Mathias, Rasika ; Sergeant, Susan ; Ruczinski, Ingo ; Torgerson, Dara G. ; Hugenschmidt, Christina E. ; Kubala, Meghan ; Vaidya, Dhananjay ; Suktitipat, Bhoom ; Ziegler, Julie T. ; Ivester, Priscilla ; Case, Douglas ; Yanek, Lisa ; Freedman, Barry I. ; Rudock, Megan E. ; Barnes, Kathleen C. ; Langefeld, Carl D. ; Becker, Lewis ; Bowden, Donald W. ; Becker, Diane M ; Chilton, Floyd H. / The impact of FADS genetic variants on ω6 polyunsaturated fatty acid metabolism in African Americans. In: BMC Genetics. 2011 ; Vol. 12.
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title = "The impact of FADS genetic variants on ω6 polyunsaturated fatty acid metabolism in African Americans",
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.",
author = "Rasika Mathias and Susan Sergeant and Ingo Ruczinski and Torgerson, {Dara G.} and Hugenschmidt, {Christina E.} and Meghan Kubala and Dhananjay Vaidya and Bhoom Suktitipat and Ziegler, {Julie T.} and Priscilla Ivester and Douglas Case and Lisa Yanek and Freedman, {Barry I.} and Rudock, {Megan E.} and Barnes, {Kathleen C.} and Langefeld, {Carl D.} and Lewis Becker and Bowden, {Donald W.} and Becker, {Diane M} and Chilton, {Floyd H.}",
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T1 - The impact of FADS genetic variants on ω6 polyunsaturated fatty acid metabolism in African Americans

AU - Mathias, Rasika

AU - Sergeant, Susan

AU - Ruczinski, Ingo

AU - Torgerson, Dara G.

AU - Hugenschmidt, Christina E.

AU - Kubala, Meghan

AU - Vaidya, Dhananjay

AU - Suktitipat, Bhoom

AU - Ziegler, Julie T.

AU - Ivester, Priscilla

AU - Case, Douglas

AU - Yanek, Lisa

AU - Freedman, Barry I.

AU - Rudock, Megan E.

AU - Barnes, Kathleen C.

AU - Langefeld, Carl D.

AU - Becker, Lewis

AU - Bowden, Donald W.

AU - Becker, Diane M

AU - Chilton, Floyd H.

PY - 2011/5/20

Y1 - 2011/5/20

N2 - 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.

AB - 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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