biostudies-literature00520Lemaitre RNNCATS NIH HHSNIA NIH HHSNCRR NIH HHSNIDDK NIH HHSNHLBI NIH HHSNHGRI NIH HHSNCI NIH HHS176-84https://www.ebi.ac.uk/biostudies/studies/S-EPMC4274065biostudies-literatureUnknown56(1)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.Journal of lipid researchGenetic loci associated with circulating levels of very long-chain saturated fatty acids.PMC4274065HHSN268201300028CU01 HG004424R01 HL043851P01 CA087969N01HC95159R01 HL059367HHSN268201100009IR01 AG023629HHSN268201100005CR01 HL060712UL1 RR025005HHSN268201100009CUL1 RR024156HHSN268201100005IHHSN268201100005GHHSN268201300027CUL1 TR000124R01 HL120393HHSN268200800007CHHSN268201100006CR01 HL035464N01HC85079P30 DK063491HHSN268201100010CR01 HL086694U01 HG004402U01 HG004446UM1 CA182913HHSN268201100011IU01 HL080295HHSN268201300026CN01HC85081HHSN268200900041CN01HC85082UM1 CA167552R01 HL085710N01HC85080HHSN268201200036CR00 HL098459HHSN268201100007CN01HC85086N01HC85083R01 CA047988R01 HL080467P01 CA055075HHSN268201100011CU01 HG004729R01 HL087652HHSN268201100007IHHSN268201300029CHHSN268201300025CN01HC95169HL105756N01HC55222R00 HL095649R01 HL034594N02HL64278HHSN268201100008CR01 HL103612R01 HL084099R01 HL105756HHSN268201100008IR01 HL087641HHSN268201100012CKabagambe EKPsaty BMWeng LCSiscovick DSChen YDDjousse LRich SSChu AYChasman DIWang LWu HFoy MSun QMozaffarian DLemaitre RNArnett DKTang WJensen MKWu JHRidker PMHu FBTsai MYSteffen LGuan WZhu JManichaikul AMcKnight BRimm EBJacobs DRFornage MKing IBFriedlander Y52falseGenetic loci associated with circulating levels of very long-chain saturated fatty acids.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.2015-01-01T00:00:00Z2015 Jan2024-10-14T22:44:30.627Z2019-03-27T01:42:13ZS-EPMC42740652537865910.1194/jlr.M052456