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.
authors: Division of General Internal Medicine, Department of Medicine, The GeneSTAR Research Program, The Johns Hopkins University, Baltimore, MD 21224, USA. rmathias@jhmi.edu
authors: Rasika A
authors: RA
authors: Mathias
authors: Susan
authors: S
authors: Sergeant
authors: Ingo
authors: I
authors: Ruczinski
authors: Dara G
authors: DG
authors: Torgerson
authors: Christina E
authors: CE
authors: Hugenschmidt
authors: Meghan
authors: M
authors: Kubala
authors: Dhananjay
authors: D
authors: Vaidya
authors: Bhoom
authors: B
authors: Suktitipat
authors: Julie T
authors: JT
authors: Ziegler
authors: Priscilla
authors: P
authors: Ivester
authors: Douglas
authors: D
authors: Case
authors: Lisa R
authors: LR
authors: Yanek
authors: Barry I
authors: BI
authors: Freedman
authors: Megan E
authors: ME
authors: Rudock
authors: Kathleen C
authors: KC
authors: Barnes
authors: Carl D
authors: CD
authors: Langefeld
authors: Lewis C
authors: LC
authors: Becker
authors: Donald W
authors: DW
authors: Bowden
authors: Diane M
authors: DM
authors: Becker
authors: Floyd H
authors: FH
authors: Chilton
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