期刊
JOURNAL OF LIPID RESEARCH
卷 56, 期 1, 页码 176-184出版社
ELSEVIER
DOI: 10.1194/jlr.M052456
关键词
arachidic acid; behenic acid; lignoceric acid; sphingolipids
资金
- National Heart, Lung, and Blood Institute [HL105756, HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, R01HL087641, R01HL59367, R01HL086694, R00HL098459, N01-HC-95159, N01-HC-95169, RR-024156]
- National Human Genome Research Institute [U01HG004402, U01-HG-004729, U01-HG-004446, U01-HG-004424]
- National Institutes of Health [HHSN268200625226C, UL1RR025005, P01 CA87969, R01 HL034594, UM1 CA167552, R01 HL35464, HL60712, CA055075]
- National Institutes of Health Roadmap for Medical Research
- National Heart, Lung, and Blood Institute with the University of Alabama at Birmingham [HHSN268201300025C, HHSN268201300026C]
- Northwestern University [HHSN268201300027C]
- University of Minnesota [HHSN268201300028C]
- Kaiser Foundation Research Institute [HHSN268201300029C]
- Johns Hopkins University School of Medicine [HHSN268200900041C]
- Intramural Research Program of the National Institute on Aging
- National Human Genome Research Institute
- National Heart, Lung, and Blood Institute (NHLBI) [R01-HL-084099]
- NHLBI [HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, U01HL080295, R01HL087652, R01HL105756, R01HL103612, R01HL120393, N02HL64278, HL043851, HL080467, R00-HL095649]
- National Institute of Neurological Disorders and Stroke
- National Institute on Aging [R01AG023629]
- National Center for Advancing Translational Sciences, CTSI [UL1TR000124]
- National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center [DK063491]
- American Diabetes Association [1-12-JF-13]
- American Heart Association [11SDG7380016]
- National Cancer Institute [CA047988]
- Donald W. Reynolds Foundation
- Fondation Leducq
- Amgen
- American Heart Association (AHA) [0735390N]
- NATIONAL CANCER INSTITUTE [P01CA087969, UM1CA167552, P01CA055075, R01CA047988, UM1CA182913] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES [UL1TR000124] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR RESEARCH RESOURCES [UL1RR025005, UL1RR024156] Funding Source: NIH RePORTER
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL035464, R01HL080467, R44HL095169, R01HL064278, R01HL059367, R01HL084099, R01HL086694, R01HL120393, R01HL103612, R01HL105756, R01HL085710, R01HL085083, R01HL087641, R01HL034594, R00HL098459, R43HL095169, R01HL043851, U01HL080295, R00HL095649, R01HL087652, R01HL060712] Funding Source: NIH RePORTER
- NATIONAL HUMAN GENOME RESEARCH INSTITUTE [U01HG004729, U01HG004424, U01HG004446, U01HG004402] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [P30DK063491] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON AGING [R01AG023629] Funding Source: NIH RePORTER
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 x 10(-13)). The CERS4 variant at rs2100944 was associated with higher levels of 20:0 (P = 2.65 x 10(-40)) and in analyses that adjusted for 20:0, with lower levels of behenic acid (P = 4.22 x 10(-26)) and lignoceric acid (P = 3.20 x 10(-21)). These novel associations suggest an inter-relationship of circulating VLSFAs and sphingolipid synthesis.
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