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Genetic loci associated with circulating levels of very long-chain saturated fatty acids.

TitleGenetic loci associated with circulating levels of very long-chain saturated fatty acids.
Publication TypeJournal Article
Year of Publication2015
AuthorsLemaitre, RN, King, IB, Kabagambe, EK, H Y Wu, J, McKnight, B, Manichaikul, A, Guan, W, Sun, Q, Chasman, DI, Foy, M, Wang, L, Zhu, J, Siscovick, DS, Tsai, MY, Arnett, DK, Psaty, BM, Djoussé, L, Chen, Y-derI, Tang, W, Weng, L-C, Wu, H, Jensen, MK, Chu, AY, Jacobs, DR, Rich, SS, Mozaffarian, D, Steffen, L, Rimm, EB, Hu, FB, Ridker, PM, Fornage, M, Friedlander, Y
JournalJ Lipid Res
Date Published2015 Jan
KeywordsCohort Studies, Fatty Acids, Genetic Loci, Genetic Variation, Genome-Wide Association Study, Humans
Abstract<p>Very long-chain saturated fatty acids (VLSFAs) are saturated fatty acids with 20 or more carbons. In contrast to the more abundant saturated fatty acids, such as palmitic acid, there is growing evidence that circulating VLSFAs may have beneficial biological properties. Whether genetic factors influence circulating levels of VLSFAs is not known. We investigated the association of common genetic variation with plasma phospholipid/erythrocyte levels of three VLSFAs by performing genome-wide association studies in seven population-based cohorts comprising 10,129 subjects of European ancestry. We observed associations of circulating VLSFA concentrations with common variants in two genes, serine palmitoyl-transferase long-chain base subunit 3 (SPTLC3), a gene involved in the rate-limiting step of de novo sphingolipid synthesis, and ceramide synthase 4 (CERS4). The SPTLC3 variant at rs680379 was associated with higher arachidic acid (20:0 , P = 5.81 × 10(-13)). The CERS4 variant at rs2100944 was associated with higher levels of 20:0 (P = 2.65 × 10(-40)) and in analyses that adjusted for 20:0, with lower levels of behenic acid (P = 4.22 × 10(-26)) and lignoceric acid (P = 3.20 × 10(-21)). These novel associations suggest an inter-relationship of circulating VLSFAs and sphingolipid synthesis.</p>
Alternate JournalJ. Lipid Res.
PubMed ID25378659
PubMed Central IDPMC4274065
Grant ListHL105756 / HL / NHLBI NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
R01 HL085710 / HL / NHLBI NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
UM1 CA182913 / CA / NCI NIH HHS / United States