Background: A recent genome-wide association study (GWAS) by our group identified 13 loci associated with the plasma triglyceride (TG) response to omega-3 (n-3) fatty acid (FA) supplementation. This study aimed to test whether single-nucleotide polymorphisms (SNPs) within the IQCJ, NXPH1, PHF17 and MYB genes are associated with the plasma TG response to an n-3 FA supplementation. Methods: A total of 208 subjects followed a 6-week n-3 FA supplementation of 5 g/day of fish oil (1.9-2.2 g of eicosapentaenoic acid and 1.1 g of docosahexaenoic acid). Measurements of plasma lipids were made before and after the supplementation. Sixty-seven tagged SNPs were selected to increase the density of markers near GWAS hits. Results: In a repeated model, independent effects of the genotype and the gene-supplementation interaction were associated with plasma TG. Genotype effects were observed with two SNPs of NXPH1, and gene-diet interactions were observed with ten SNPs of IQCJ, four SNPs of NXPH1 and three SNPs of MYB. Positive and negative responders showed different genotype frequencies with nine SNPs of IQCJ, two SNPs of NXPH1 and two SNPs of MYB. Conclusion: Fine mapping in GWAS-associated loci allowed the identification of SNPs partly explaining the large interindividual variability observed in plasma TG levels in response to an n-3 FA supplementation.

Marik PE, Varon J: Omega-3 dietary supplements and the risk of cardiovascular events: a systematic review. Clin Cardiol 2009;32:365-372.
Miller M, Stone NJ, Ballantyne C, Bittner V, Criqui MH, Ginsberg HN, Goldberg AC, Howard WJ, Jacobson MS, Kris-Etherton PM, Lennie TA, Levi M, Mazzone T, Pennathur S: Triglycerides and cardiovascular disease: a scientific statement from the American Heart Association. Circulation 2011;123:2292-2333.
Cormier H, Rudkowska I, Paradis AM, Thifault E, Garneau V, Lemieux S, Couture P, Vohl MC: Association between polymorphisms in the fatty acid desaturase gene cluster and the plasma triacylglycerol response to an n-3 PUFA supplementation. Nutrients 2012;4:1026-1041.
Caslake MJ, Miles EA, Kofler BM, Lietz G, Curtis P, Armah CK, Kimber AC, Grew JP, Farrell L, Stannard J, Napper FL, Sala-Vila A, West AL, Mathers JC, Packard C, Williams CM, Calder PC, Minihane AM: Effect of sex and genotype on cardiovascular biomarker response to fish oils: the FINGEN study. Am J Clin Nutr 2008;88:618-629.
Masson LF, McNeill G, Avenell A: Genetic variation and the lipid response to dietary intervention: a systematic review. Am J Clin Nutr 2003;77:1098-1111.
Minihane AM, Khan S, Leigh-Firbank EC, Talmud P, Wright JW, Murphy MC, Griffin BA, Williams CM: APOE polymorphism and fish oil supplementation in subjects with an atherogenic lipoprotein phenotype. Arterioscler Thromb Vasc Biol 2000;20:1990-1997.
Tai ES, Demissie S, Cupples LA, Corella D, Wilson PW, Schaefer EJ, Ordovas JM: Association between the PPARA L162V polymorphism and plasma lipid levels: the Framingham Offspring Study. Arterioscler Thromb Vasc Biol 2002;22:805-810.
Lindi V, Schwab U, Louheranta A, Laakso M, Vessby B, Hermansen K, Storlien L, Riccardi G, Rivellese A: Impact of the Pro12Ala polymorphism of the PPAR-γ2 gene on serum triacylglycerol response to n-3 fatty acid supplementation. Mol Genet Metab 2003;79:52-60.
Thifault E, Cormier H, Bouchard-Mercier A, Rudkowska I, Paradis AM, Garneau V, Ouellette C, Lemieux S, Couture P, Vohl MC: Effects of age, sex, body mass index and APOE genotype on cardiovascular biomarker response to an n-3 polyunsaturated fatty acid supplementation. J Nutrigenet Nutrigenomics 2013;6:73-82.
Rudkowska I, Guenard F, Julien P, Couture P, Lemieux S, Barbier O, Calder PC, Minihane AM, Vohl MC: Genome-wide association study of the plasma triglyceride response to an n-3 polyunsaturated fatty acid supplementation. J Lipid Res 2014;55:1245-1253.
Kwasnicka-Crawford DA, Carson AR, Scherer SW: IQCJ-SCHIP1, a novel fusion transcript encoding a calmodulin-binding IQ motif protein. Biochem Biophys Res Commun 2006;350:890-899.
Martin PM, Carnaud M, Garcia del CG, Irondelle M, Irinopoulou T, Girault JA, Dargent B, Goutebroze L: Schwannomin-interacting protein-1 isoform IQCJ-SCHIP-1 is a late component of nodes of Ranvier and axon initial segments. J Neurosci 2008;28:6111-6117.
Missler M, Hammer RE, Sudhof TC: Neurexophilin binding to α-neurexins. A single LNS domain functions as an independently folding ligand-binding unit. J Biol Chem 1998;273:34716-34723.
Missler M, Sudhof TC: Neurexophilins form a conserved family of neuropeptide-like glycoproteins. J Neurosci 1998;18:3630-3638.
Reissner C, Stahn J, Breuer D, Klose M, Pohlentz G, Mormann M, Missler M: Dystroglycan binding to α-neurexin competes with neurexophilin-1 and neuroligin in the brain. J Biol Chem 2014;289:27585-27603.
Zhou MI, Foy RL, Chitalia VC, Zhao J, Panchenko MV, Wang H, Cohen HT: Jade-1, a candidate renal tumor suppressor that promotes apoptosis. Proc Natl Acad Sci USA 2005;102:11035-11040.
Doyon Y, Cayrou C, Ullah M, Landry AJ, Cote V, Selleck W, Lane WS, Tan S, Yang XJ, Cote J: ING tumor suppressor proteins are critical regulators of chromatin acetylation required for genome expression and perpetuation. Mol Cell 2006;21:51-64.
Foy RL, Song IY, Chitalia VC, Cohen HT, Saksouk N, Cayrou C, Vaziri C, Cote J, Panchenko MV: Role of Jade-1 in the histone acetyltransferase (HAT) HBO1 complex. J Biol Chem 2008;283:28817-28826.
Siriwardana NS, Meyer R, Havasi A, Dominguez I, Panchenko MV: Cell cycle-dependent chromatin shuttling of HBO1-JADE1 histone acetyl transferase (HAT) complex. Cell Cycle 2014;13:1885-1901.
Vanhee S, De MK, Van CY, Verstichel G, Van RN, Menten B, Velghe I, Philippe J, De BD, Lambrecht BN, Taghon T, Leclercq G, Kerre T, Vandekerckhove B: In vitro human embryonic stem cell hematopoiesis mimics MYB-independent yolk sac hematopoiesis. Haematologica 2015;100:157-166.
Sarvaiya PJ, Schwartz JR, Hernandez CP, Rodriguez PC, Vedeckis WV: Role of c-Myb in the survival of pre B-cell acute lymphoblastic leukemia and leukemogenesis. Am J Hematol 2012;87:969-976.
Costa AF, Altemani A, Garcia-Inc, Fresno F, Suarez C, Llorente JL, Hermsen M: Analysis of Myb oncogene in transformed adenoid cystic carcinomas reveals distinct pathways of tumor progression. Lab Invest 2014;94:692-702.
Burstein M, Samaille J: On a rapid determination of the cholesterol bound to the serum α- and β-lipoproteins (in French). Clin Chim Acta 1960;5:609.
McNamara JR, Schaefer EJ: Automated enzymatic standardized lipid analyses for plasma and lipoprotein fractions. Clin Chim Acta 1987;166:1-8.
Leiter LA, Betteridge DJ, Farnier M, Guyton JR, Lin J, Shah A, Johnson-Levonas AO, Brudi P: Lipid-altering efficacy and safety profile of combination therapy with ezetimibe/statin vs. statin monotherapy in patients with and without diabetes: an analysis of pooled data from 27 clinical trials. Diabetes Obes Metab 2011;13:615-628.
Kraja AT, Borecki IB, Tsai MY, Ordovas JM, Hopkins PN, Lai CQ, Frazier-Wood AC, Straka RJ, Hixson JE, Province MA, Arnett DK: Genetic analysis of 16 NMR-lipoprotein fractions in humans, the GOLDN study. Lipids 2013;48:155-165.
Kiefer D, Pantuso T: Omega-3 fatty acids: an update emphasizing clinical use. Agro Food Ind Hi Tech 2012;23:10-13.
Delerive P, Fruchart JC, Staels B: Peroxisome proliferator-activated receptors in inflammation control. J Endocrinol 2001;169:453-459.
Bragt MC, Mensink RP: Comparison of the effects of n-3 long chain polyunsaturated fatty acids and fenofibrate on markers of inflammation and vascular function, and on the serum lipoprotein profile in overweight and obese subjects. Nutr Metab Cardiovasc Dis 2012;22:966-973.
Lee M, Saver JL, Towfighi A, Chow J, Ovbiagele B: Efficacy of fibrates for cardiovascular risk reduction in persons with atherogenic dyslipidemia: a meta-analysis. Atherosclerosis 2011;217:492-498.
Frazier-Wood AC, Aslibekyan S, Borecki IB, Hopkins PN, Lai CQ, Ordovas JM, Straka RJ, Tiwari HK, Arnett DK: Genome-wide association study indicates variants associated with insulin signaling and inflammation mediate lipoprotein responses to fenofibrate. Pharmacogenet Genomics 2012;22:750-757.
Kondo A, Muranaka Y, Ohta I, Notsu K, Manabe M, Kotani K, Saito K, Maekawa M, Kanno T: Relationship between triglyceride concentrations and LDL size evaluated by malondialdehyde-modified LDL. Clin Chem 2001;47:893-900.
Comuzzie AG, Cole SA, Laston SL, Voruganti VS, Haack K, Gibbs RA, Butte NF: Novel genetic loci identified for the pathophysiology of childhood obesity in the hispanic population. PLoS One 2012;7:e51954.
Zhao L, Ye P, Gonda TJ: The MYB proto-oncogene suppresses monocytic differentiation of acute myeloid leukemia cells via transcriptional activation of its target gene GFI1. Oncogene 2014;33:4442-4449.
Gross CM, Kramer J, Pfeufer A, Dietz R, Gessner R, Praus M: The intron 6 G/T polymorphism of c-myb oncogene and the risk for coronary in-stent restenosis. Basic Res Cardiol 2004;99:309-314.
Lai WK, Kan MY: Homocysteine-induced endothelial dysfunction. Ann Nutr Metab 2015;67:1-12.
Melen E, Himes BE, Brehm JM, Boutaoui N, Klanderman BJ, Sylvia JS, Lasky-Su J: Analyses of shared genetic factors between asthma and obesity in children. J Allergy Clin Immunol 2010;126:631-637.
Xu H, Inouye M, Hines ER, Collins JF, Ghishan FK: Transcriptional regulation of the human NaPi-IIb cotransporter by EGF in Caco-2 cells involves c-myb. Am J Physiol Cell Physiol 2003;284:C1262-C1271.
Chen Y, Liu J, Xu H, Luo Z, Zhang C: Overexpression of the c-myb but not its leukemogenic mutant DNA-binding domain increased adipogenic differentiation in mesenchymal stem cells. Biochem Biophys Res Commun 2011;407:202-206.
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