title: Differences in arachidonic acid levels and fatty acid desaturase (FADS) gene variants in African Americans and European Americans with diabetes or the metabolic syndrome.
abstract: Over the past 50 years, increases in dietary n-6 PUFA, such as linoleic acid, have been hypothesised to cause or exacerbate chronic inflammatory diseases. The present study examines an individual's innate capacity to synthesise n-6 long-chain PUFA (LC-PUFA) with respect to the fatty acid desaturase (FADS) locus in Americans of African and European descent with diabetes or the metabolic syndrome. Compared with European Americans (EAm), African Americans (AfAm) exhibited markedly higher serum levels of arachidonic acid (AA) (EAm 7·9 (sd 2·1), AfAm 9·8 (sd 1·9) % of total fatty acids; P < 2·29 × 10⁻⁹) and the AA:n-6-precursor fatty acid ratio, which estimates FADS1 activity (EAm 5·4 (sd 2·2), AfAm 6·9 (sd 2·2); P = 1·44 × 10⁻⁵). In all, seven SNP mapping to the FADS locus revealed strong association with AA, EPA and dihomo-γ-linolenic acid (DGLA) in the EAm. Importantly, EAm homozygous for the minor allele (T) had significantly lower AA levels (TT 6·3 (sd 1·0); GG 8·5 (sd 2·1); P = 3·0 × 10⁻⁵) and AA:DGLA ratios (TT 3·4 (sd 0·8), GG 6·5 (sd 2·3); P = 2·2 × 10⁻⁷) but higher DGLA levels (TT 1·9 (sd 0·4), GG 1·4 (sd 0·4); P = 3·3 × 10⁻⁷) compared with those homozygous for the major allele (GG). Allele frequency patterns suggest that the GG genotype at rs174537 (associated with higher circulating levels of AA) is much higher in AfAm (0·81) compared with EAm (0·46). Similarly, marked differences in rs174537 genotypic frequencies were observed in HapMap populations. These data suggest that there are probably important differences in the capacity of different populations to synthesise LC-PUFA. These differences may provide a genetic mechanism contributing to health disparities between populations of African and European descent.
authors: The Center for Botanical Lipids and Inflammatory Disease Prevention, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
authors: Susan
authors: S
authors: Sergeant
authors: Christina E
authors: CE
authors: Hugenschmidt
authors: Megan E
authors: ME
authors: Rudock
authors: Julie T
authors: JT
authors: Ziegler
authors: Priscilla
authors: P
authors: Ivester
authors: Hannah C
authors: HC
authors: Ainsworth
authors: Dhananjay
authors: D
authors: Vaidya
authors: L Douglas
authors: LD
authors: Case
authors: Carl D
authors: CD
authors: Langefeld
authors: Barry I
authors: BI
authors: Freedman
authors: Donald W
authors: DW
authors: Bowden
authors: Rasika A
authors: RA
authors: Mathias
authors: Floyd H
authors: FH
authors: Chilton
mesh_terms: D015126:8,11,14-Eicosatrienoic Acid / Q000097:blood; D001741:Black or African American; D000368:Aged; D016718:Arachidonic Acid / Q000097:blood*; D000090943:Delta-5 Fatty Acid Desaturase; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000208:ethnology / Q000235:genetics*; D015118:Eicosapentaenoic Acid / Q000097:blood; D005192:Family Health; D044943:Fatty Acid Desaturases / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000208:ethnology / Q000235:genetics*; D008875:Middle Aged; D005810:Multigene Family; D020641:Polymorphism, Single Nucleotide; D035781:Siblings; D014481:United States; D044465:White People
chemical_list: D000090943:Delta-5 Fatty Acid Desaturase; D016718:Arachidonic Acid; D015118:Eicosapentaenoic Acid; D044943:Fatty Acid Desaturases; C000716847:FADS1 protein, human; C533241:FADS2 protein, human; D015126:8,11,14-Eicosatrienoic Acid