Mathias RA, Sergeant S, Ruczinski I, Torgerson DG, Hugenschmidt CE, Kubala M, Vaidya D, Suktitipat B, Ziegler JT, Ivester P, Case D, Yanek LR, Freedman BI, Rudock ME, Barnes KC, Langefeld CD, Becker LC, Bowden DW, Becker DM, Chilton FH (2011) BMC Genet. 12(1) 50. [Epub ahead of print]
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=1.35x10-48) and lower DGLA levels (p=9.80x10-11) 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= 2.85x10-16 in African Americans, 2.68x10-23 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.
The huge excess of omega-6 over omega-3 fats in modern western-type diets is now thought to underlie a very wide range of physical and mental health disorders. These new findings show that people of African ancestry may be at particularly high risk for such health problems when consuming such a diet, owing to interactions between normal genetic variation and dietary fat intake.
Humans have only a limited ability to convert the simplest forms of omega-3 and omega-6 polyunstaurated fats (found in vegetable oils, nuts and seeds) into the highly unsaturated forms on which brain and body health depend.
This new research shows that on average, Americans of African descent are better at this conversion than Americans of European descent, owing to normal genetic variations affecting the enzymes involved.
Unfortunately, this can be disadvantageous to health when consuming a modern, western-type diet, which provides a huge excess of the simplest omega-6 fats, and very little omega-3. In brief, 'good converters' are more likely to accumulate a correspondong excess of the longer-chain omega-6 than 'poor converters'. This in turn increases their risks of inflammatory disorders, heart disease and stroke, and many other degenerative conditions.
See also 'Ancestry plays vital role in nutrition and disease' for an accessible summary of these findings and their implications