02945nas a2200589 4500008004100000022001400041245009400055210006900149260001300218300001100231490000700242520132000249653001901569653001601588653001701604653002201621653003401643653001101677100002401688700001901712700002501731700001801756700002201774700002101796700001701817700001201834700002301846700001901869700001301888700001701901700002401918700002101942700002101963700002001984700001802004700002102022700001802043700001802061700001502079700002202094700001902116700002102135700002102156700002502177700001702202700001802219700001702237700002002254700002002274700002502294856003602319 2015 eng d a1539-726200aGenetic loci associated with circulating levels of very long-chain saturated fatty acids.0 aGenetic loci associated with circulating levels of very longchai c2015 Jan a176-840 v563 a
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.
10aCohort Studies10aFatty Acids10aGenetic Loci10aGenetic Variation10aGenome-Wide Association Study10aHumans1 aLemaitre, Rozenn, N1 aKing, Irena, B1 aKabagambe, Edmond, K1 aH Y Wu, Jason1 aMcKnight, Barbara1 aManichaikul, Ani1 aGuan, Weihua1 aSun, Qi1 aChasman, Daniel, I1 aFoy, Millennia1 aWang, Lu1 aZhu, Jingwen1 aSiscovick, David, S1 aTsai, Michael, Y1 aArnett, Donna, K1 aPsaty, Bruce, M1 aDjoussé, Luc1 aChen, Yii-der, I1 aTang, Weihong1 aWeng, Lu-Chen1 aWu, Hongyu1 aJensen, Majken, K1 aChu, Audrey, Y1 aJacobs, David, R1 aRich, Stephen, S1 aMozaffarian, Dariush1 aSteffen, Lyn1 aRimm, Eric, B1 aHu, Frank, B1 aRidker, Paul, M1 aFornage, Myriam1 aFriedlander, Yechiel uhttps://chs-nhlbi.org/node/6615