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Title: Amino acid change in the carbohydrate response element binding protein is associated with lower triglycerides and myocardial infarction incidence depending on level of adherence to the mediterranean diet in the PREDIMED trial
Authors: Ortega-Azorín, Carolina
Sorlí, Jose V.
Estruch, Ramón
Asensio, Eva M.
Coltell, Oscar
González, José I.
Martínez-González, Miguel Ángel
Ros, Emilio
Salas-Salvadó, Jordi
Fitó, Montserrat
Arós, Fernando
Lapetra, José
Serra-Majem, Lluís 
Ruiz-Gutiérrez, Valentina
Gómez-Gracia, Enrique
Fiol, Miquel
Flores, Gemma
Pintó, Xavier
Saiz, Carmen
Ordovás, José M.
Corella, Dolores
Keywords: Coronary-Artery-Disease
Lipid Concentrations
Hepatic Steatosis
Mlxipl Gene, et al
Issue Date: 2014
Publisher: 1942-325X
Journal: Circulation: Cardiovascular Genetics 
Abstract: Background: A variant (rs3812316, C771G, and Gln241His) in the MLXIPL (Max-like protein X interacting protein-like) gene encoding the carbohydrate response element binding protein has been associated with lower triglycerides. However, its association with cardiovascular diseases and gene-diet interactions modulating these traits are unknown. Methods and Results: We studied 7166 participants in the PREvención with DIeta MEDiterránea trial testing a Mediterranean diet (MedDiet) intervention versus a control diet for cardiovascular prevention, with a median follow-up of 4.8 years. Diet, lipids, MLXIPL polymorphisms, and cardiovascular events were assessed. Data were analyzed at baseline and longitudinally. We used multivariable-adjusted Cox regression to estimate hazard ratios for cardiovascular outcomes. The MLXIPL-rs3812316 was associated with lower baseline triglycerides (P=5.5×10-5) and lower hypertriglyceridemia (odds ratio, 0.73; 95% confidence interval [CI], 0.63-0.85; P=1.4×10-6 in G-carriers versus CC). This association was modulated by baseline adherence to MedDiet. When adherence to MedDiet was high, the protection was stronger (odds ratio, 0.63; 95% CI, 0.51-0.77; P=8.6×10-6) than when adherence to MedDiet was low (odds ratio, 0.88; 95% CI, 0.70-1.09; P=0.219). Throughout the follow-up, both the MLXIPL-rs3812316 (P=3.8×10-6) and the MedDiet intervention (P=0.030) were significantly associated with decreased triglycerides. Likewise in G-carriers MedDiet intervention was associated with greater total cardiovascular risk reduction and specifically for myocardial infarction. In the MedDiet, but not in the control group, we observed lower myocardial infarction incidence in G-carriers versus CC (hazard ratios, 0.34; 95% CI, 0.12-0.93; P=0.036 and 0.90; 95% CI, 0.35-2.33; P=0.830, respectively). Conclusions: Our novel results suggest that MedDiet enhances the triglyceride-lowering effect of the MLXIPL-rs3812316 variant and strengthens its protective effect on myocardial infarction incidence. © 2014 American Heart Association, Inc.
ISSN: 1942-325X
DOI: 10.1161/CIRCGENETICS.113.000301
Source: Circulation: Cardiovascular Genetics[ISSN 1942-325X],v. 7, p. 49-58
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