MicroRNA-410 Regulated Lipoprotein Lipase Variant rs13702 Is Associated With Stroke Incidence and Modulated by Diet in the Randomized Controlled PREDIMED Trial

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

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 (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.

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.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions*
  • Aged
  • Aged, 80 and over
  • Cohort Studies
  • Diet, Mediterranean*
  • Female
  • Follow-Up Studies
  • Genetic Association Studies
  • Humans
  • Hypertriglyceridemia / diet therapy*
  • Hypertriglyceridemia / genetics
  • Hypertriglyceridemia / metabolism
  • Hypertriglyceridemia / physiopathology
  • Incidence
  • Lipoprotein Lipase / chemistry
  • Lipoprotein Lipase / genetics*
  • Lipoprotein Lipase / metabolism
  • Male
  • MicroRNAs / metabolism*
  • Middle Aged
  • Nuts
  • Olive Oil
  • Plant Oils / therapeutic use
  • Polymorphism, Single Nucleotide*
  • Risk Factors
  • Spain / epidemiology
  • Stroke / epidemiology
  • Stroke / etiology
  • Stroke / prevention & control*
  • Survival Analysis

Substances

  • 3' Untranslated Regions
  • MIRN410 microRNA, human
  • MicroRNAs
  • Olive Oil
  • Plant Oils
  • LPL protein, human
  • Lipoprotein Lipase

Associated data

  • ISRCTN/ISRCTN35739639