期刊论文详细信息
Lipids in Health and Disease
Gene-diet interactions with polymorphisms of the MGLL gene on plasma low-density lipoprotein cholesterol and size following an omega-3 polyunsaturated fatty acid supplementation: a clinical trial
Marie-Claude Vohl1  Patrick Couture1  Benoit Lamarche2  Simone Lemieux2  Iwona Rudkowska1  Catherine Ouellette2 
[1] CHU de Québec Research Center – Endocrinology and Nephrology, Quebec, QC, Canada;Institute of Nutrition and Functional Foods (INAF), Laval University, 2440 Hochelaga Blvd., Quebec, QC, Canada
关键词: LDL particle size;    LDL cholesterol;    MGLL;    Nutrigenomics;    Omega-3 polyunsaturated fatty acids;   
Others  :  828363
DOI  :  10.1186/1476-511X-13-86
 received in 2014-03-31, accepted in 2014-05-15,  发布年份 2014
PDF
【 摘 要 】

Background

Omega-3 (n-3) polyunsaturated fatty acid (PUFA) consumption increases low-density lipoprotein (LDL) cholesterol (C) concentrations and particle size. Studies showed that individuals with large, buoyant LDL particles have decreased risk of cardiovascular diseases. However, a large inter-individual variability is observed in LDL particle size. Genetic factors may explain the variability of LDL-C concentrations and particle size after an n-3 PUFA supplementation. The monoglyceride lipase (MGLL) enzyme, encoded by the MGLL gene, plays an important role in lipid metabolism, especially lipoprotein metabolism. The aim of this study was to investigate if polymorphisms (SNPs) of the MGLL gene influence the variability of LDL-C and LDL particle size in response to an n-3 PUFA supplementation.

Methods

210 subjects completed the study. They consumed 5 g/d of a fish oil supplement (1.9-2.2 g eicosapentaenoic acid and 1.1 g docosaexaenoic acid) during 6 weeks. Plasma lipids were measured before and after the supplementation period and 18 SNPs of the MGLL gene, covering 100% of common genetic variations (minor allele frequency ≥0.05), have been genotyped using TaqMan technology (Life Technologies Inc., Burlington, ON, CA).

Results

Following the n-3 PUFA supplementation, 55% of subjects increased their LDL-C levels. In a model including the supplementation, genotype and supplementation*genotype effects, gene-diet interaction effects on LDL-C concentrations (rs782440, rs6776142, rs555183, rs6780384, rs6787155 and rs1466571) and LDL particle size (rs9877819 and rs13076593) were observed for the MGLL gene SNPs (p < 0.05).

Conclusion

SNPs within the MGLL gene may modulate plasma LDL-C levels and particle size following an n-3 PUFA supplementation. This trial was registered at clinicaltrials.gov as NCT01343342.

【 授权许可】

   
2014 Ouellette et al.; licensee BioMed Central Ltd.

【 预 览 】
附件列表
Files Size Format View
20140714001923550.pdf 408KB PDF download
Figure 2. 15KB Image download
Figure 1. 69KB Image download
【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】
  • [1]Dyerberg J, Banga H, Stoffersena E, Moncadab S, Vaneb J: Eicosapentaenoic acid and prevention of thrombosis and atherosclerosis? Lancet 1978, 2:117-119.
  • [2]Psota TL, Gebauer SK, Kris-Etherton P: Dietary omega-3 fatty acid intake and cardiovascular risk. Am J Cardiol 2006, 98:3I-18I.
  • [3]Nicholson T, Khademi H, Moghadasian MH: The role of marine n-3 fatty acids in improving cardiovascular health: a review. Food Funct 2013, 4:357-365.
  • [4]von Schacky C: Prophylaxis of atherosclerosis with marine omega-3 fatty acids. A comprehensive strategy. Ann Intern Med 1987, 107:890-899.
  • [5]Davidson MH: Mechanisms for the hypotriglyceridemic effect of marine omega-3 fatty acids. AmJ Cardiol 2006, 98:27i-33i.
  • [6]Harris WS, Bulchandani D: Why do omega-3 fatty acids lower serum triglycerides? Curr Opin Lipidol 2006, 17:387-393.
  • [7]Hokanson JE, Austin MA: Plasma triglyceride level is a risk factor for cardiovascular disease independent of high-density lipoprotein cholesterol level: a meta-analysis of population-based prospective studies. J CardiovascRisk 1996, 3:213-219.
  • [8]Baum SJ, Kris-Etherton PM, Willett WC, Lichtenstein AH, Rudel LL, Maki KC, Whelan J, Ramsden CE, Block RC: Fatty acids in cardiovascular health and disease: a comprehensive update. J Clin Lipidol 2012, 6:216-234.
  • [9]Jacobson TA, Glickstein SB, Rowe JD, Soni PN: Effects of eicosapentaenoic acid and docosahexaenoic acid on low-density lipoprotein cholesterol and other lipids: a review. J ClinLipidol 2012, 6:5-18.
  • [10]Eslick GD, Howe PR, Smith C, Priest R, Bensoussan A: Benefits of fish oil supplementation in hyperlipidemia: a systematic review and meta-analysis. Int J Cardiol 2009, 136:4-16.
  • [11]Wilson PW, D'Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB: Prediction of coronary heart disease using risk factor categories. Circulation 1998, 97:1837-1847.
  • [12]Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report Circulation 2002, 106:3143-3421.
  • [13]Berneis K, Rizzo M: LDL size: does it matter? SwissMedWkly 2004, 134:720-724.
  • [14]Lamarche B, Lemieux I, Despres JP: The small, dense LDL phenotype and the risk of coronary heart disease: epidemiology, patho-physiology and therapeutic aspects. Diabetes Metab 1999, 25:199-211.
  • [15]St-Pierre AC, Ruel IL, Cantin B, Dagenais GR, Bernard PM, Despres JP, Lamarche B: Comparison of various electrophoretic characteristics of LDL particles and their relationship to the risk of ischemic heart disease. Circulation 2001, 104:2295-2299.
  • [16]Baumstark MW, Frey I, Berg A, Keul J: Influence of n-3 fatty acids from fish oils on concentration of high- and low-density lipoprotein subfractions and their lipid and apolipoprotein composition. Clin Biochem 1992, 25:338-340.
  • [17]Griffin MD, Sanders TA, Davies IG, Morgan LM, Millward DJ, Lewis F, Slaughter S, Cooper JA, Miller GJ, Griffin BA: Effects of altering the ratio of dietary n-6 to n-3 fatty acids on insulin sensitivity, lipoprotein size, and postprandial lipemia in men and postmenopausal women aged 45–70 y: the OPTILIP Study. Am J Clin Nutr 2006, 84:1290-1298.
  • [18]Griffin BA: The effect of n-3 fatty acids on low density lipoprotein subfractions. Lipids 2001, 36(Suppl):S91-S97.
  • [19]Agouridis AP, Kostapanos MS, Tsimihodimos V, Kostara C, Mikhailidis DP, Bairaktari ET, Tselepis AD, Elisaf MS: Effect of rosuvastatin monotherapy or in combination with fenofibrate or omega-3 fatty acids on lipoprotein subfraction profile in patients with mixed dyslipidaemia and metabolic syndrome. Int J Clin Pract 2012, 66:843-853.
  • [20]Lee MW, Park JK, Hong JW, Kim KJ, Shin DY, Ahn CW, Song YD, Cho HK, Park SW, Lee EJ: Beneficial effects of omega-3 fatty acids on low density lipoprotein particle size in patients with type 2 diabetes already under statin therapy. Diabetes Metab J 2013, 37:207-211.
  • [21]Kelley DS, Siegel D, Vemuri M, Mackey BE: Docosahexaenoic acid supplementation improves fasting and postprandial lipid profiles in hypertriglyceridemic men. Am J Clin Nutr 2007, 86:324-333.
  • [22]Suzukawa M, Abbey M, Howe PR, Nestel PJ: Effects of fish oil fatty acids on low density lipoprotein size, oxidizability, and uptake by macrophages. J Lipid Res 1995, 36:473-484.
  • [23]Oelrich B, Dewell A, Gardner CD: Effect of fish oil supplementation on serum triglycerides, LDL cholesterol and LDL subfractions in hypertriglyceridemic adults. Nutr Metab Cardiovasc Dis 2013, 23:350-357.
  • [24]Rivellese AA, Maffettone A, Vessby B, Uusitupa M, Hermansen K, Berglund L, Louheranta A, Meyer BJ, Riccardi G: Effects of dietary saturated, monounsaturated and n-3 fatty acids on fasting lipoproteins, LDL size and post-prandial lipid metabolism in healthy subjects. Atherosclerosis 2003, 167:149-158.
  • [25]Patti L, Maffettone A, Iovine C, Marino LD, Annuzzi G, Riccardi G, Rivellese AA: Long-term effects of fish oil on lipoprotein subfractions and low density lipoprotein size in non-insulin-dependent diabetic patients with hypertriglyceridemia. Atherosclerosis 1999, 146:361-367.
  • [26]Hellstrand S, Sonestedt E, Ericson U, Gullberg B, Wirfalt E, Hedblad B, Orho-Melander M: Intake levels of dietary long-chain PUFAs modify the association between genetic variation in FADS and LDL-C. J Lipid Res 2012, 53:1183-1189.
  • [27]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. AmJ ClinNutr 2008, 88:618-629.
  • [28]Volcik KA, Nettleton JA, Ballantyne CM, Boerwinkle E: Peroxisome proliferator-activated receptor [alpha] genetic variation interacts with n-6 and long-chain n-3 fatty acid intake to affect total cholesterol and LDL-cholesterol concentrations in the atherosclerosis risk in communities study. Am J Clin Nutr 2008, 87:1926-1931.
  • [29]Joffe YT, van der Merwe L, Carstens M, Collins M, Jennings C, Levitt NS, Lambert EV, Goedecke JH: Tumor necrosis factor-alpha gene -308 G/A polymorphism modulates the relationship between dietary fat intake, serum lipids, and obesity risk in black South African women. J Nutr 2010, 140:901-907.
  • [30]Karlsson M, Reue K, Xia YR, Lusis AJ, Langin D, Tornqvist H, Holm C: Exon-intron organization and chromosomal localization of the mouse monoglyceride lipase gene. Gene 2001, 272:11-18.
  • [31]Chanda PK, Gao Y, Mark L, Btesh J, Strassle BW, Lu P, Piesla MJ, Zhang MY, Bingham B, Uveges A, Kowal D, Garbe D, Kouranova EV, Ring RH, Bates B, Pangalos MN, Kennedy JD, Whiteside GT, Samad TA: Monoacylglycerol lipase activity is a critical modulator of the tone and integrity of the endocannabinoid system. Mol Pharmacol 2010, 78:996-1003.
  • [32]Goulet J, Nadeau G, Lapointe A, Lamarche B, Lemieux S: Validity and reproducibility of an interviewer-administered food frequency questionnaire for healthy French-Canadian men and women. NutrJ 2004, 3:13.
  • [33]CW C: CWBC Standardization of Anthropometric Measurements. In The Airlie (VA) Consensus Conference. Champaign: Human Kinetics Publishers; 1988.
  • [34]McNamara JR, Schaefer EJ: Automated enzymatic standardized lipid analyses for plasma and lipoprotein fractions. ClinChimActa 1987, 166:1-8.
  • [35]Burstein M, Samaille J: [On a rapid determination of the cholesterol bound to the serum alpha- and beta-lipoproteins]. ClinChimActa 1960, 5:609.
  • [36]Albers JJ, Warnick GR, Wiebe D, King P, Steiner P, Smith L, Breckenridge C, Chow A, Kuba K, Weidman S, Arnett H, Wood P, Shlagenhaft A: Multi-laboratory comparison of three heparin-Mn2+ precipitation procedures for estimating cholesterol in high-density lipoprotein. ClinChem 1978, 24:853-856.
  • [37]Friedewald WT, Levy RI, Fredrickson DS: Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. ClinChem 1972, 18:499-502.
  • [38]Laurell CB: Quantitative estimation of proteins by electrophoresis in agarose gel containing antibodies. AnalBiochem 1966, 15:45-52.
  • [39]Bouchard-Mercier A, Godin G, Lamarche B, Perusse L, Vohl MC: Effects of peroxisome proliferator-activated receptors, dietary fat intakes and gene-diet interactions on peak particle diameters of low-density lipoproteins. J Nutrigenet Nutrigenomics 2011, 4:36-48.
  • [40]Tchernof A, Lamarche B, Prud'Homme D, Nadeau A, Moorjani S, Labrie F, Lupien PJ, Despres JP: The dense LDL phenotype. Association with plasma lipoprotein levels, visceral obesity, and hyperinsulinemia in men. Diabetes Care 1996, 19:629-637.
  • [41]Schaefer EJ, Lamon-Fava S, Ausman LM, Ordovas JM, Clevidence BA, Judd JT, Goldin BR, Woods M, Gorbach S, Lichtenstein AH: Individual variability in lipoprotein cholesterol response to National Cholesterol Education Program Step 2 diets. Am J Clin Nutr 1997, 65:823-830.
  • [42]Bays HE, Tighe AP, Sadovsky R, Davidson MH: Prescription omega-3 fatty acids and their lipid effects: physiologic mechanisms of action and clinical implications. Expert Rev Cardiovasc Ther 2008, 6:391-409.
  • [43]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.
  • [44]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.
  • [45]Harris WS: n-3 fatty acids and serum lipoproteins: human studies. AmJ ClinNutr 1997, 65:1645S-1654S.
  • [46]Faghihnia N, Tsimikas S, Miller ER, Witztum JL, Krauss RM: Changes in lipoprotein(a), oxidized phospholipids, and LDL subclasses with a low-fat high-carbohydrate diet. J Lipid Res 2010, 51:3324-3330.
  • [47]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.
  • [48]Harismendy O, Bansal V, Bhatia G, Nakano M, Scott M, Wang X, Dib C, Turlotte E, Sipe JC, Murray SS, Deleuze JF, Bafna V, Topol EJ, Frazer KA: Population sequencing of two endocannabinoid metabolic genes identifies rare and common regulatory variants associated with extreme obesity and metabolite level. Genome Biol 2010, 11:R118. BioMed Central Full Text
  • [49]Kunos G, Osei-Hyiaman D, Liu J, Godlewski G, Batkai S: Endocannabinoids and the control of energy homeostasis. J Biol Chem 2008, 283:33021-33025.
  • [50]Cote M, Matias I, Lemieux I, Petrosino S, Almeras N, Despres JP, Di MV: Circulating endocannabinoid levels, abdominal adiposity and related cardiometabolic risk factors in obese men. IntJ Obes(Lond) 2007, 31:692-699.
  • [51]Engeli S, Bohnke J, Feldpausch M, Gorzelniak K, Janke J, Batkai S, Pacher P, Harvey-White J, Luft FC, Sharma AM, Jordan J: Activation of the peripheral endocannabinoid system in human obesity. Diabetes 2005, 54:2838-2843.
  • [52]Alberti KG, Zimmet P, Shaw J: Metabolic syndrome–a new world-wide definition. A consensus statement from the international diabetes federation. Diabet Med 2006, 23:469-480.
  • [53]Mantyselka P, Kautiainen H, Saltevo J, Wurtz P, Soininen P, Kangas AJ, Ala-Korpela M, Vanhala M: Weight change and lipoprotein particle concentration and particle size: a cohort study with 6.5-year follow-up. Atherosclerosis 2012, 223:239-243.
  • [54]Taschler U, Radner FPW, Heier C, Schreiber R, Schweiger M, Schoiswohl G, Preiss-Landl K, Jaeger D, Reiter B, Koefeler HC, Wojciechowski J, Theussl C, Penninger JM, Lass A, Haemmerle G, Zechner R, Zimmermann R: Monoglyceride lipase deficiency in mice impairs lipolysis and attenuates diet-induced insulin resistance. J Biol Chem 2011, 286:17467-17477.
  文献评价指标  
  下载次数:9次 浏览次数:7次