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
Circ Cardiovasc Genet. 2014 Feb;7(1):49-58. doi: 10.1161/CIRCGENETICS.113.000301. Epub 2014 Jan 21.
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.
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).
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.
URL: www.controlled-trials.com. Unique Identifier: ISRCTN35739639.
编码碳水化合物反应元件结合蛋白的MLXIPL（Max样蛋白X相互作用蛋白样）基因中的一个变体（rs3812316，C771G，谷氨酰胺241组氨酸）与较低的甘油三酯水平相关。然而，其与心血管疾病的关联以及调节这些性状的基因-饮食相互作用尚不清楚。
我们在预防地中海饮食（PREDIMED）试验中研究了7166名参与者，该试验测试了地中海饮食（MedDiet）干预与对照饮食对心血管疾病的预防作用，中位随访时间为4.8年。评估了饮食、血脂、MLXIPL基因多态性和心血管事件。在基线和纵向对数据进行了分析。我们使用多变量调整的Cox回归来估计心血管结局的风险比。MLXIPL-rs3812316与较低的基线甘油三酯水平（P = 5.5×10⁻⁵）和较低的高甘油三酯血症相关（优势比，0.73；95%置信区间[CI]，0.63 - 0.85；G携带者与CC相比，P = 1.4×10⁻⁶）。这种关联受到基线时对MedDiet依从性的调节。当对MedDiet的依从性高时，保护作用更强（优势比，0.63；95% CI，0.51 - 0.77；P = 8.6×10⁻⁶），而当对MedDiet的依从性低时（优势比，0.88；95% CI，0.70 - 1.09；P = 0.219）。在整个随访过程中，MLXIPL-rs3812316（P = 3.8×10⁻⁶）和MedDiet干预（P = 0.030）均与甘油三酯降低显著相关。同样，在G携带者中，MedDiet干预与更大程度的总体心血管风险降低相关，特别是对于心肌梗死。在MedDiet组而非对照组中，我们观察到G携带者与CC相比心肌梗死发生率较低（风险比分别为0.34；95% CI，0.12 - 0.93；P = 0.036和0.90；95% CI，0.35 - 2.33；P = 0.830）。
我们的新结果表明，MedDiet增强了MLXIPL-rs3812316变体的降甘油三酯作用，并加强了其对心肌梗死发生率的保护作用。
