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Am J Clin Nutr. 2014 Aug;100(2):719-31. doi: 10.3945/ajcn.113.076992. Epub 2014 Jul 2.

MicroRNA-410 regulated lipoprotein lipase variant rs13702 is associated with stroke incidence and modulated by diet in the randomized controlled PREDIMED trial.

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  • 1From the Department of Preventive Medicine and Public Health, School of Medicine, University of Valencia, Valencia, Spain (DC, JVS, CO-A, OP, and EMA); CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain (DC, JVS, RE, OC, CO-A, OP, MÁM-G, MB, M Fitó, FA, JL, EMA, GTS, LS-M, CM-B, VR-G, M Fiol, EV, XP, and ER); Department of Internal Medicine, Hospital Clinic, IDIBAPS, Barcelona, Spain (RE); Department of Computer Languages and Systems, University Jaume I, Castellon, Spain (OC); Department of Preventive Medicine and Public Health, School of Medicine, University of Navarra, Pamplona, Spain (MÁM-G); Human Nutrition Unit, Faculty of Medicine, IISPV, University Rovira i Virgili, Reus, Spain (MB); Cardiovascular Epidemiology Unit, Municipal Institut for Medical Research, Barcelona, Spain (M Fitó); Department of Cardiology, Hospital Txagorritxu, Vitoria, Spain (FA); Department of Family Medicine, Primary Care Division of Sevilla, Sevilla, Spain (JL); Department of Biochemistry and Molecular Biology, Clinical Analysis Service-CDB, HGUV, University of Valencia, Valencia, Spain (GTS); Department of Clinical Sciences, University of Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain (LS-M); Department of Epidemiology, School of Medicine, University of Málaga, Málaga, Spain (CM-B); Instituto de la Grasa, Consejo Superior Investigaciones Cientificas, Seville (VR-G); University Institute for Health Sciences Investigation, Hospital Son Dureta, Palma de Mallorca, Spain (M Fiol); Primary Care Division, Catalan Institute of Health, Barcelona, Spain (EV); Lipids and Vascular Risk Unit, Internal Medicine, Hospital Universitario de Bellvitge, Hospitalet de Llobregat, Barcelona, Spain (XP); Nutrition and Genomics Laboratory, JM-USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA (KR, JMO); Lipid Clinic, Endocrinology and Nutrition Service, Institut d'Investigacions Biomèdiques August Pi Sunyer, Hospita



MicroRNAs have emerged as important epigenetic regulators in cardiovascular diseases (CVDs). Using an observational meta-analysis design, we previously characterized a gain-of-function microRNA-410 target site polymorphism (rs13702T>C) in the 3'untranslated region of the lipoprotein lipase (LPL) gene. The C allele was associated with lower triglycerides, and this association was modulated by fat intake.


We aimed to extend our findings by assessing the interaction between the rs13702 polymorphism and fat intake on triglycerides at baseline and longitudinally by using a dietary intervention design. We also examined as a primary outcome the association of this variant with CVD incidence and its modulation by the Mediterranean diet (MedDiet).


We studied 7187 participants in the PREDIMED (Prevención con Dieta Mediterránea) randomized trial that tested a MedDiet intervention compared with a control diet, with a median 4.8-y follow-up. LPL polymorphisms and triglycerides were determined and CVD assessed. Gene-diet interactions for triglycerides were analyzed at baseline (n = 6880) and after a 3-y intervention (n = 4131). Oxidative stress parameters were investigated in a subsample.


The rs13702T>C polymorphism was strongly associated with lower triglycerides in C allele carriers and interacted synergistically with dietary monounsaturated (P = 0.038) and unsaturated fat intake (P = 0.037), decreasing triglycerides at baseline. By 3 y, we observed a gene-diet interaction (P = 0.025) in which the C allele was associated with a greater reduction in triglycerides after intervention with MedDiet, high in unsaturated fat. Although the polymorphism was associated with lower stroke risk (HR: 0.74; 95% CI: 0.57, 0.97; P = 0.029 per C allele), this association reached statistical significance only in the MedDiet intervention (HR: 0.58; 95% CI: 0.37, 0.91; P = 0.019 in C compared with TT carriers), not in the control group (HR: 0.94; 95% CI: 0.55, 1.59; P = 0.805).


We report a novel association between a microRNA target site variant and stroke incidence, which is modulated by diet in terms of decreasing triglycerides and possibly stroke risk in rs13702 C allele carriers after a high-unsaturated fat MedDiet intervention.

© 2014 American Society for Nutrition.

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