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
; 100(2): 719-31, 2014 Aug.
Article
em En
| MEDLINE
| ID: mdl-24990426
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.
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
1_ASSA2030
/
2_ODS3
Base de dados:
MEDLINE
Assunto principal:
Hipertrigliceridemia
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Regiões 3' não Traduzidas
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Acidente Vascular Cerebral
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Polimorfismo de Nucleotídeo Único
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MicroRNAs
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Dieta Mediterrânea
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Lipase Lipoproteica
Tipo de estudo:
Clinical_trials
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Etiology_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
País/Região como assunto:
Europa
Idioma:
En
Revista:
Am J Clin Nutr
Ano de publicação:
2014
Tipo de documento:
Article