Comparative Analyses of Disease Risk Genes Belonging to the Acyl-CoA Synthetase Medium-Chain (ACSM) Family in Human Liver and Cell Lines
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The human ACSM1, 2A and B, 3, and 5 genes, located on chromosome 16p12-13, encode for enzymes catalyzing the activation of medium-chain length fatty acids. Association studies have linked several polymorphisms of these genes to traits of insulin resistance syndrome. In our study, ACSM transcripts showed 3 to >400-fold higher expression levels in human liver when compared to cell lines by qRT-PCR. This difference was also evident at the protein level, as shown for ACSM2. In liver, ACSM2 was the most abundant transcript, showing sixfold (vs. ACSM3) to >300-fold higher expression levels (vs. ACSM1). Mitochondrial localization of the ACSM2 protein and the presence of an N-terminal targeting sequence were shown by GFP-tagging. We have shown ACSM2B to be the predominant transcript in human liver, and genetic variations of this gene could therefore play an important role in disease susceptibility.
KeywordsAcyl-CoA synthetase medium-chain (ACSM) Medium-chain fatty acid Liver HuH-7 HepG2
We thank Daniela Hallack for excellent technical assistance. This study was financially supported by the Federal Ministry of Education and Research (Project: Fat and Metabolism: gene variation, gene regulation, and gene function; AZ 0312823A/B).
- Haketa A, Soma M, Nakayama T, Sato M, Kosuge K, Aoi N, Matsumoto K (2004) Two medium-chain acyl-coenzyme A synthetase genes, SAH and MACS1, are associated with plasma high-density lipoprotein cholesterol levels, but they are not associated with essential hypertension. J Hypertens 22:1903–1907PubMedCrossRefGoogle Scholar
- Lindner I, Rubin D, Helwig U, Nitz I, Hampe J, Schreiber S, Schrezenmeir J, Doring F (2006) The L513S polymorphism in medium-chain acyl-CoA synthetase 2 (MACS2) is associated with risk factors of the metabolic syndrome in a Caucasian study population. Mol Nutr Food Res 50:270–274PubMedCrossRefGoogle Scholar
- Loftus BJ, Kim UJ, Sneddon VP, Kalush F, Brandon R, Fuhrmann J, Mason T, Crosby ML, Barnstead M, Cronin L, Deslattes Mays A, Cao Y, Xu RX, Kang HL, Mitchell S, Eichler EE, Harris PC, Venter JC, Adams MD (1999) Genome duplications and other features in 12 Mb of DNA sequence from human chromosome 16p and 16q. Genomics 60:295–308PubMedCrossRefGoogle Scholar
- Martin J, Han C, Gordon LA, Terry A, Prabhakar S, She X, Xie G, Hellsten U, Chan YM, Altherr M, Couronne O, Aerts A, Bajorek E, Black S, Blumer H, Branscomb E, Brown NC, Bruno WJ, Buckingham JM, Callen DF, Campbell CS, Campbell ML, Campbell EW, Caoile C, Challacombe JF, Chasteen LA, Chertkov O, Chi HC, Christensen M, Clark LM, Cohn JD, Denys M, Detter JC, Dickson M, Dimitrijevic-Bussod M, Escobar J, Fawcett JJ, Flowers D, Fotopulos D, Glavina T, Gomez M, Gonzales E, Goodstein D, Goodwin LA, Grady DL, Grigoriev I, Groza M, Hammon N, Hawkins T, Haydu L, Hildebrand CE, Huang W, Israni S, Jett J, Jewett PB, Kadner K, Kimball H, Kobayashi A, Krawczyk MC, Leyba T, Longmire JL, Lopez F, Lou Y, Lowry S, Ludeman T, Manohar CF, Mark GA, McMurray KL, Meincke LJ, Morgan J, Moyzis RK, Mundt MO, Munk AC, Nandkeshwar RD, Pitluck S, Pollard M, Predki P, Parson-Quintana B, Ramirez L, Rash S, Retterer J, Ricke DO, Robinson DL, Rodriguez A, Salamov A, Saunders EH, Scott D, Shough T, Stallings RL, Stalvey M, Sutherland RD, Tapia R, Tesmer JG, Thayer N, Thompson LS, Tice H, Torney DC, Tran-Gyamfi M, Tsai M, Ulanovsky LE, Ustaszewska A, Vo N, White PS, Williams AL, Wills PL, Wu JR, Wu K, Yang J, Dejong P, Bruce D, Doggett NA, Deaven L, Schmutz J, Grimwood J, Richardson P, Rokhsar DS, Eichler EE, Gilna P, Lucas SM, Myers RM, Rubin EM, Pennacchio LA (2004) The sequence and analysis of duplication-rich human chromosome 16. Nature 432:988–994PubMedCrossRefGoogle Scholar
- Telgmann R, Brand E, Nicaud V, Hagedorn C, Beining K, Schonfelder J, Brink-Spalink V, Schmidt-Petersen K, Matanis T, Vischer P, Nofer JR, Hasenkamp S, Plouin PF, Drouet L, Cambien F, Paul M, Tiret L, Brand-Herrmann SM (2007) SAH gene variants are associated with obesity-related hypertension in Caucasians: the PEGASE Study. J Hypertens 25:557–564PubMedCrossRefGoogle Scholar
- Tikhonoff V, Staessen JA, Kuznetsova T, Thijs L, Hasenkamp S, Baumer V, Stolarz K, Seidlerova J, Filipovsky J, Nikitin Y, Peleska J, Kawecka-Jaszcz K, Casiglia E, Brand-Herrmann SM, Brand E (2008) SAH gene variants revisited in the European project on genes in hypertension. J Hypertens 26:244–250PubMedCrossRefGoogle Scholar