British Journal of Nutrition

Human and Clinical Nutrition

Differences in arachidonic acid levels and fatty acid desaturase (FADS) gene variants in African Americans and European Americans with diabetes or the metabolic syndrome

Susan Sergeanta1a2, Christina E. Hugenschmidta3, Megan E. Rudocka4, Julie T. Zieglera5, Priscilla Ivestera1a6, Hannah C. Ainswortha1a6, Dhananjay Vaidyaa7, L. Douglas Casea5, Carl D. Langefelda5, Barry I. Freedmana8, Donald W. Bowdena2a3a4, Rasika A. Mathiasa7a9 and Floyd H. Chiltona1a6 c1

a1 The Center for Botanical Lipids and Inflammatory Disease Prevention, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA

a2 Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA

a3 Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA

a4 Center for Human Genomics, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA

a5 Division of Public Health Sciences, Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA

a6 Department of Physiology/Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA

a7 Division of General Internal Medicine, Department of Medicine, The Johns Hopkins University, Baltimore, MD 21224, USA

a8 Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA

a9 Division of Allergy and Clinical Immunology, Department of Medicine, The Johns Hopkins University, Baltimore, MD 21224, USA

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.

(Received December 10 2010)

(Revised April 11 2011)

(Accepted May 05 2011)

(Online publication July 04 2011)

Correspondence:

c1 Corresponding author: Dr Floyd H. Chilton, fax +1 336 716 8501, email schilton@wakehealth.edu

Footnotes

Abbreviations: AA, arachidonic acid; DGLA, dihomo-γ-linolenic acid; DHS, Diabetes Heart Study; FADS, fatty acid desaturase; GLA, γ-linolenic acid; LA, linoleic acid; LC-PUFA, long-chain PUFA; LD, linkage disequilibrium

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