The Impact of FADS Genetic Variants on ω6 Polyunsaturated Fatty Acid Metabolism in African Americans

Overview

Journal BMC Genet

Publisher Biomed Central

Specialties Biotechnology
Molecular Biology

Date 2011 May 24

PMID 21599946

Citations 74

Authors

Rasika A Mathias

Susan Sergeant

Ingo Ruczinski

Dara G Torgerson

Christina E Hugenschmidt

Meghan Kubala

Dhananjay Vaidya

Bhoom Suktitipat

Julie T Ziegler

Priscilla Ivester

Douglas Case

Lisa R Yanek

Barry I Freedman

Megan E Rudock

Kathleen C Barnes

Carl D Langefeld

Lewis C Becker

Donald W Bowden

Diane M Becker

Floyd H Chilton

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Optimal Pair Matching Combined with Machine Learning Predicts a Significant Reduction in Myocardial Infarction Risk in African Americans Following Omega-3 Fatty Acid Supplementation.

Sun S, Hara A, Johnstone L, Hallmark B, Watkins J, Thomson C Nutrients. 2024; 16(17).

PMID: 39275249 PMC: 11397525. DOI: 10.3390/nu16172933.

The role of polyunsaturated fatty acids in the neurobiology of major depressive disorder and suicide risk.

Sublette M, Daray F, Gananca L, Shaikh S Mol Psychiatry. 2023; 29(2):269-286.

PMID: 37993501 DOI: 10.1038/s41380-023-02322-6.

Genome-wide association studies and fine-mapping identify genomic loci for n-3 and n-6 polyunsaturated fatty acids in Hispanic American and African American cohorts.

Yang C, Veenstra J, Bartz T, Pahl M, Hallmark B, Chen Y Commun Biol. 2023; 6(1):852.

PMID: 37587153 PMC: 10432561. DOI: 10.1038/s42003-023-05219-w.

Associations of fatty acids composition and estimated desaturase activities in erythrocyte phospholipids with biochemical and clinical indicators of cardiometabolic risk in non-diabetic Serbian women: the role of level of adiposity.

Sarac I, Debeljak-Martacic J, Takic M, Stevanovic V, Milesevic J, Zekovic M Front Nutr. 2023; 10:1065578.

PMID: 37545582 PMC: 10397414. DOI: 10.3389/fnut.2023.1065578.

Histone H2A Lys130 acetylation epigenetically regulates androgen production in prostate cancer.

Nguyen T, Sridaran D, Chouhan S, Weimholt C, Wilson A, Luo J Nat Commun. 2023; 14(1):3357.

PMID: 37296155 PMC: 10256812. DOI: 10.1038/s41467-023-38887-7.

References

Malerba G, Schaeffer L, Xumerle L, Klopp N, Trabetti E, Biscuola M . SNPs of the FADS gene cluster are associated with polyunsaturated fatty acids in a cohort of patients with cardiovascular disease. Lipids. 2008; 43(4):289-99. DOI: 10.1007/s11745-008-3158-5. View

Emken E, Adlof R, Gulley R . Dietary linoleic acid influences desaturation and acylation of deuterium-labeled linoleic and linolenic acids in young adult males. Biochim Biophys Acta. 1994; 1213(3):277-88. DOI: 10.1016/0005-2760(94)00054-9. View

Lattka E, Eggers S, Moeller G, Heim K, Weber M, Mehta D . A common FADS2 promoter polymorphism increases promoter activity and facilitates binding of transcription factor ELK1. J Lipid Res. 2009; 51(1):182-91. PMC: 2789778. DOI: 10.1194/jlr.M900289-JLR200. View

Tanaka T, Shen J, Abecasis G, Kisialiou A, Ordovas J, Guralnik J . Genome-wide association study of plasma polyunsaturated fatty acids in the InCHIANTI Study. PLoS Genet. 2009; 5(1):e1000338. PMC: 2613033. DOI: 10.1371/journal.pgen.1000338. View

Das U . Essential fatty acids: biochemistry, physiology and pathology. Biotechnol J. 2006; 1(4):420-39. DOI: 10.1002/biot.200600012. View

Cordain L, Eaton S, Sebastian A, Mann N, Lindeberg S, Watkins B . Origins and evolution of the Western diet: health implications for the 21st century. Am J Clin Nutr. 2005; 81(2):341-54. DOI: 10.1093/ajcn.81.2.341. View

Rzehak P, Heinrich J, Klopp N, Schaeffer L, Hoff S, Wolfram G . Evidence for an association between genetic variants of the fatty acid desaturase 1 fatty acid desaturase 2 ( FADS1 FADS2) gene cluster and the fatty acid composition of erythrocyte membranes. Br J Nutr. 2008; 101(1):20-6. DOI: 10.1017/S0007114508992564. View

Burdge G . Metabolism of alpha-linolenic acid in humans. Prostaglandins Leukot Essent Fatty Acids. 2006; 75(3):161-8. DOI: 10.1016/j.plefa.2006.05.013. View

Marquardt A, Stohr H, White K, Weber B . cDNA cloning, genomic structure, and chromosomal localization of three members of the human fatty acid desaturase family. Genomics. 2000; 66(2):175-83. DOI: 10.1006/geno.2000.6196. View

10.

Martinez M . Tissue levels of polyunsaturated fatty acids during early human development. J Pediatr. 1992; 120(4 Pt 2):S129-38. DOI: 10.1016/s0022-3476(05)81247-8. View

11.

Xie L, Innis S . Genetic variants of the FADS1 FADS2 gene cluster are associated with altered (n-6) and (n-3) essential fatty acids in plasma and erythrocyte phospholipids in women during pregnancy and in breast milk during lactation. J Nutr. 2008; 138(11):2222-8. DOI: 10.3945/jn.108.096156. View

12.

Zeger S, Liang K . Longitudinal data analysis for discrete and continuous outcomes. Biometrics. 1986; 42(1):121-30. View

13.

Lattka E, Illig T, Heinrich J, Koletzko B . FADS gene cluster polymorphisms: important modulators of fatty acid levels and their impact on atopic diseases. J Nutrigenet Nutrigenomics. 2009; 2(3):119-28. DOI: 10.1159/000235559. View

14.

Steinberg G, SLATON Jr W, HOWTON D, Mead J . Metabolism of essential fatty acids. IV. Incorporation of linoleate into arachidonic acid. J Biol Chem. 1956; 220(1):257-64. View

15.

Mead J, Steinberg G, HOWTON D . Metabolism of essential fatty acids; incorporation of acetate into arachidonic acid. J Biol Chem. 1953; 205(2):683-9. View

16.

Buetow K, Edmonson M, MacDonald R, Clifford R, Yip P, Kelley J . High-throughput development and characterization of a genomewide collection of gene-based single nucleotide polymorphism markers by chip-based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Proc Natl Acad Sci U S A. 2001; 98(2):581-4. PMC: 14630. DOI: 10.1073/pnas.98.2.581. View

17.

Albert M, Glynn R, Buring J, Ridker P . C-reactive protein levels among women of various ethnic groups living in the United States (from the Women's Health Study). Am J Cardiol. 2004; 93(10):1238-42. DOI: 10.1016/j.amjcard.2004.01.067. View

18.

Gabriel S, Schaffner S, Nguyen H, Moore J, Roy J, Blumenstiel B . The structure of haplotype blocks in the human genome. Science. 2002; 296(5576):2225-9. DOI: 10.1126/science.1069424. View

19.

Mead J, HOWTON D . Metabolism of essential fatty acids. VII. Conversion of gamma-linolenic acid to arachidonic acid. J Biol Chem. 1957; 229(2):575-82. View

20.

Schaeffer L, Gohlke H, Muller M, Heid I, Palmer L, Kompauer I . Common genetic variants of the FADS1 FADS2 gene cluster and their reconstructed haplotypes are associated with the fatty acid composition in phospholipids. Hum Mol Genet. 2006; 15(11):1745-56. DOI: 10.1093/hmg/ddl117. View