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FADS genetic variants and omega-6 polyunsaturated fatty acid metabolism in a homogeneous island population.
J Lipid Res. 2010 Sep; 51(9):2766-74.JL

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 x 10(-7) - 1.7 x 10(-8)) among other PUFAs, but the strongest associations were with the ratio measuring FADS1 activity in the omega-6 series (P = 2.11 x 10(-13) - 1.8 x 10(-20)). The minor allele across all SNPs was consistently associated with decreased omega-6 PUFAs, with the exception of dihomo-gamma-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 Delta-5 desaturase enzymatic step likely regulate the efficiency of conversion of medium-chain PUFAs to potentially inflammatory PUFAs, such as AA.

Authors+Show Affiliations

Division of General Internal Medicine, The Johns Hopkins University, Baltimore, MD, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20562440

Citation

Mathias, Rasika A., et al. "FADS Genetic Variants and Omega-6 Polyunsaturated Fatty Acid Metabolism in a Homogeneous Island Population." Journal of Lipid Research, vol. 51, no. 9, 2010, pp. 2766-74.
Mathias RA, Vergara C, Gao L, et al. FADS genetic variants and omega-6 polyunsaturated fatty acid metabolism in a homogeneous island population. J Lipid Res. 2010;51(9):2766-74.
Mathias, R. A., Vergara, C., Gao, L., Rafaels, N., Hand, T., Campbell, M., Bickel, C., Ivester, P., Sergeant, S., Barnes, K. C., & Chilton, F. H. (2010). FADS genetic variants and omega-6 polyunsaturated fatty acid metabolism in a homogeneous island population. Journal of Lipid Research, 51(9), 2766-74. https://doi.org/10.1194/jlr.M008359
Mathias RA, et al. FADS Genetic Variants and Omega-6 Polyunsaturated Fatty Acid Metabolism in a Homogeneous Island Population. J Lipid Res. 2010;51(9):2766-74. PubMed PMID: 20562440.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - FADS genetic variants and omega-6 polyunsaturated fatty acid metabolism in a homogeneous island population. AU - Mathias,Rasika A, AU - Vergara,Candelaria, AU - Gao,Li, AU - Rafaels,Nicholas, AU - Hand,Tracey, AU - Campbell,Monica, AU - Bickel,Carol, AU - Ivester,Priscilla, AU - Sergeant,Susan, AU - Barnes,Kathleen C, AU - Chilton,Floyd H, Y1 - 2010/06/19/ PY - 2010/6/22/entrez PY - 2010/6/22/pubmed PY - 2011/2/15/medline SP - 2766 EP - 74 JF - Journal of lipid research JO - J. Lipid Res. VL - 51 IS - 9 N2 - 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 x 10(-7) - 1.7 x 10(-8)) among other PUFAs, but the strongest associations were with the ratio measuring FADS1 activity in the omega-6 series (P = 2.11 x 10(-13) - 1.8 x 10(-20)). The minor allele across all SNPs was consistently associated with decreased omega-6 PUFAs, with the exception of dihomo-gamma-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 Delta-5 desaturase enzymatic step likely regulate the efficiency of conversion of medium-chain PUFAs to potentially inflammatory PUFAs, such as AA. SN - 1539-7262 UR - https://www.unboundmedicine.com/medline/citation/20562440/FADS_genetic_variants_and_omega_6_polyunsaturated_fatty_acid_metabolism_in_a_homogeneous_island_population_ L2 - http://www.jlr.org/cgi/pmidlookup?view=long&pmid=20562440 DB - PRIME DP - Unbound Medicine ER -