FADS genetic variants and ω-6 polyunsaturated fatty acid metabolism in a homogeneous island population

Rasika Mathias, Candelaria Vergara, Li Gao, Nicholas Rafaels, Tracey Hand, Monica Campbell, Carol Bickel, Priscilla Ivester, Susan Sergeant, Kathleen C. Barnes, Floyd H. Chilton

Research output: Contribution to journalArticle

Abstract

Long-chain polyunsaturated fatty acids (PUFA) orchestrate immunity and inflammation through their capacity to be converted to potent inflammatory mediators. We assessed associations of FADS gene cluster polymorphisms and fasting serum PUFA concentrations in a fully ascertained, geographically isolated founder population of European descent. Concentrations of 22 PUFAs were determined by gas chromatography, of which ten fatty acids and five ratios defining FADS1 and FADS2 activity were tested for genetic association against 16 single nucleotide polymorphisms (SNP) in 224 individuals. A cluster of SNPs in tight linkage disequilibrium in the FADS1 gene (rs174537, rs174545, rs174546, rs174553, rs174556, rs174561, rs174568, and rs99780) were strongly associated with arachidonic acid (AA) (P = 5.8 × 10-7 - 1.7 × 10-8) among other PUFAs, but the strongest associations were with the ratio measuring FADS1 activity in the ω-6 series (P = 2.11 × 10-13 - 1.8 × 10-20). The minor allele across all SNPs was consistently associated with decreased ω-6 PUFAs, with the exception of dihomo-γ-linoleic acid (DHGLA), where the minor allele was consistently associated with increased levels. Our findings in a geographically isolated population with a homogenous dietary environment suggest that variants in the Δ-5 desaturase enzymatic step likely regulate the efficiency of conversion of medium-chain PUFAs to potentially inflammatory PUFAs, such as AA.

Original languageEnglish (US)
Pages (from-to)2766-2774
Number of pages9
JournalJournal of Lipid Research
Volume51
Issue number9
DOIs
StatePublished - Sep 2010

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Polymorphism
Unsaturated Fatty Acids
Islands
Arachidonic Acid
Metabolism
Single Nucleotide Polymorphism
Genes
Linoleic Acid
Alleles
Gas chromatography
Population
Fatty Acids
Nucleotides
Linkage Disequilibrium
Association reactions
Multigene Family
Gas Chromatography
Immunity
Fasting
Inflammation

Keywords

  • Fatty acid desaturase
  • Genetic association
  • Isolated population

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Endocrinology

Cite this

FADS genetic variants and ω-6 polyunsaturated fatty acid metabolism in a homogeneous island population. / Mathias, Rasika; Vergara, Candelaria; Gao, Li; Rafaels, Nicholas; Hand, Tracey; Campbell, Monica; Bickel, Carol; Ivester, Priscilla; Sergeant, Susan; Barnes, Kathleen C.; Chilton, Floyd H.

In: Journal of Lipid Research, Vol. 51, No. 9, 09.2010, p. 2766-2774.

Research output: Contribution to journalArticle

Mathias, R, Vergara, C, Gao, L, Rafaels, N, Hand, T, Campbell, M, Bickel, C, Ivester, P, Sergeant, S, Barnes, KC & Chilton, FH 2010, 'FADS genetic variants and ω-6 polyunsaturated fatty acid metabolism in a homogeneous island population', Journal of Lipid Research, vol. 51, no. 9, pp. 2766-2774. https://doi.org/10.1194/jlr.M008359
Mathias, Rasika ; Vergara, Candelaria ; Gao, Li ; Rafaels, Nicholas ; Hand, Tracey ; Campbell, Monica ; Bickel, Carol ; Ivester, Priscilla ; Sergeant, Susan ; Barnes, Kathleen C. ; Chilton, Floyd H. / FADS genetic variants and ω-6 polyunsaturated fatty acid metabolism in a homogeneous island population. In: Journal of Lipid Research. 2010 ; Vol. 51, No. 9. pp. 2766-2774.
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AU - Hand, Tracey

AU - Campbell, Monica

AU - Bickel, Carol

AU - Ivester, Priscilla

AU - Sergeant, Susan

AU - Barnes, Kathleen C.

AU - Chilton, Floyd H.

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