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.

Conflict of interest statement

F.H.C. has published books with Rodale and Simon and Schuster and is a founder and consultant to GeneSmart Health, Inc., which may be partially related to his research. These potential conflicts of interest have been disclosed to Wake Forest School of Medicine and to outside sponsors and are institutionally managed. No other authors have a conflict of interest.

Figures

Figure 1

Serum Fatty Acid Distributions of n-6 Polyunsaturated Fatty Acids (PUFA) in African American (AfAm; n = 63; 41.3% male; age = 61.0±10.1) and European American (EAm; n = 166; 42.7% male; age = 68.2±10.5) adults with diabetic/metabolic syndrome from the Diabetes Heart Study (DHS) study (a–d). Normal kernel density estimation (implemented in S-Plus) was used to obtain estimates of the probability density functions that show the distribution of subjects having circulating n-6 PUFAs as a function of percent of total fatty acids by race. The product-precursor ratios (mean±sd, e–g) of circulating fatty acids were used to estimate (e) fatty acid desaturase 2 (FADS2; gamma-linolenic acid to linoleic acid ratio, GLA/LA), (f) elongase (dihomogamma-linolenic acid to gamma-linolenic acid ratio, DGLA/GLA), and (g) fatty acid desaturase 1 (FADS1; arachidonic acid to dihomogamma-linolenic acid ratio, AA/DGLA) enzymatic efficiencies for each population. Linear mixed models were used for statistical analyses to assess the racial difference in the fatty acids and ratios adjusting for sex, age and familial relationships (See Methods). Resultant p values are shown.

Figure 2

Fatty acid trait distribution differences between European American (n = 159; a–c) and African American (n = 63; c–e) adults with diabetic/metabolic syndrome from the Diabetes Heart Study (DHS) study based on genotype at rs174537. Each sample is represented by a single symbol in red for European Americans or blue for African Americans at each genotype. Sample means and 95% confidence interval for the sample mean are shown as the horizontal black line and bars, respectively. Fatty acid data are the percent of total fatty acids and the arachidonic acid to dihomogamma-linolenic acid ratio (AA/DLGA) was calculated from fatty acid mass. Values that are significantly different are indicated (*, p<0.01; **, p<0.00001) based on two-tailed, pair wise T test within populations. Genotypic data were unavailable for seven European American subjects.

Figure 3

Distributions of rs174537 genotype frequency in ten HapMap-derived global populations (defined in text) and the Diabetes Heart Study (DHS) African American (AfAm) and European American (EAm) subpopulations (at arrowheads) are ranked from low to high for the homozygous major allele (GG, blue).