Research article
The impact of FADS genetic variants on ω6 polyunsaturated fatty acid metabolism in African Americans
Author affiliations
1 Division of General Internal Medicine, Department of Medicine, The GeneSTAR Research Program, The Johns Hopkins University, 1830 E. Monument St., Baltimore, MD 21224, USA
2 Division of Allergy and Clinical Immunology, Department of Medicine, The Johns Hopkins University, 1830 E. Monument St., Baltimore, MD 21224, USA
3 Department of Biochemistry, Medical Center Blvd., Wake Forest University Health Sciences, Winston-Salem, NC 27157, USA
4 Wake Forest Center for Botanical Lipids and Inflammatory Disease Prevention, Medical Center Blvd., Wake Forest University Health Sciences, Winston-Salem, NC 27157, USA
5 Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, 615 N. Wolfe Street, Baltimore, MD 21224, USA
6 Department of Human Genetics, 920 E. 58th St., University of Chicago, Chicago, IL 60637, USA
7 Center for Diabetes Research, Wake Forest University Health Sciences, Medical Center Blvd., Winston-Salem, NC 27157, USA
8 Division of Public Health Sciences, Department of Biostatistical Sciences, Medical Center Blvd., Wake Forest University Health Sciences, Winston-Salem, NC 27157, USA
9 Department of Physiology/Pharmacology, Wake Forest University Health Sciences, Medical Center Blvd., Winston-Salem, NC 27157, USA
10 Department of Internal Medicine, Wake Forest University Health Sciences, Medical Center Blvd., Winston-Salem, NC 27157, USA
11 Center for Human Genomics, Wake Forest University Health Sciences, Medical Center Blvd., Winston-Salem, NC 27157, USA
Citation and License
BMC Genetics 2011, 12:50 doi:10.1186/1471-2156-12-50
Published: 20 May 2011Abstract
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.
