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Title: MicroRNA-410 regulated lipoprotein lipase variant rs13702 is associated with stroke incidence and modulated by diet in the randomized controlled PREDIMED trial
Authors: Corella, Dolores
Sorlí, Jose V.
Estruch, Ramon
Coltell, Oscar
Ortega-Azorín, Carolina
Portolés, Olga
Martínez-González, Miguel Ángel
Bulló, Mónica
Fitó, Montserrat
Arós, Fernando
Lapetra, José
Asensio, Eva M.
Sáez, Guillermo T.
Serra-Majem, Lluís 
Muñoz-Bravo, Carlos
Ruiz-Gutiérrez, Valentina
Fiol, Miquel
Vinyoles, Ernest
Pintó, Xavier
Richardson, Kris
Ros, Emilio
Ordovás, Jose M.
Keywords: Cardiovascular Risk-Factors
Target Site Polymorphisms
Type-2 Diabetes-Mellitus
Mediterranean Population, et al
Issue Date: 2014
Publisher: 0002-9165
Journal: The American journal of clinical nutrition 
Abstract: Background: 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.Objectives: 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).Design: We studied 7187 participants in the PREDIMED (Prevencion con Dieta Mediterranea) 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.Results: 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).Conclusion: 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.
ISSN: 0002-9165
DOI: 10.3945/ajcn.113.076992
Source: American Journal of Clinical Nutrition[ISSN 0002-9165],v. 100, p. 719-731
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