载脂蛋白C-III、n-3多不饱和脂肪酸以及心脏病患者中“胰岛素抵抗型”T-455C APOC3基因多态性：基因-饮食相互作用实例

Apolipoprotein C-III, n-3 polyunsaturated fatty acids, and "insulin-resistant" T-455C APOC3 gene polymorphism in heart disease patients: example of gene-diet interaction.

作者信息

Olivieri Oliviero, Martinelli Nicola, Sandri Marco, Bassi Antonella, Guarini Patrizia, Trabetti Elisabetta, Pizzolo Francesca, Girelli Domenico, Friso Simonetta, Pignatti Pier Franco, Corrocher Roberto

机构信息

Unit of Internal Medicine, Department of Clinical and Experimental Medicine, University of Verona, Verona, Italy.

出版信息

Clin Chem. 2005 Feb;51(2):360-7. doi: 10.1373/clinchem.2004.040477. Epub 2004 Dec 2.

DOI:10.1373/clinchem.2004.040477

PMID:15576429

Abstract

BACKGROUND

Apolipoprotein C-III (apo C-III) is a marker of cardiovascular disease risk associated with triglyceride (TG)-rich lipoproteins. The T-455C polymorphism in the insulin-responsive element of the APOC3 gene influences TG and apo C-III concentrations. Long-chain n-3 polyunsaturated fatty acids (PUFAs) contained in fish have well-known apo C-III-lowering properties.

METHODS

We investigated the possibility of an interactive effect between the APOC3 gene variant and erythrocyte n-3 PUFAs, suitable markers of dietary intake of fatty acids, on apo C-III concentrations in a population of 848 heart disease patients who had coronary angiography.

RESULTS

In the population as a whole, apo C-III concentrations were significantly inversely correlated with total erythrocyte PUFAs, but the correlation was not significant when only -455CC homozygous individuals were taken into account. In the total population and in subgroups with the -455TT and -455CT genotypes, the relative proportions of individuals presenting with increased apo C-III (i.e., above the 75th percentile value calculated on the entire population after exclusion of individuals taking lipids-lowering medications) decreased progressively as the n-3 PUFA and docosahexaenoic acid concentrations increased. The opposite situation was observed in the homozygous -455CC subgroup, in whom increasing erythrocyte n-3 PUFA and docosahexaenoic acid concentrations were associated with higher proportions of individuals with high apo C-III. A formal interactive effect between genotype and n-3 PUFAs was confirmed even after adjustment for possible confounding variables [age, sex, body mass index, smoking, coronary artery disease (CAD)/CAD-free status, or use of lipid-lowering medications] by logistic models.

CONCLUSION

Patients homozygous for the -455C APOC3 variant are poorly responsive to the apo C-III-lowering effects of n-3 PUFAs.

摘要

背景

载脂蛋白C-III（apo C-III）是与富含甘油三酯（TG）的脂蛋白相关的心血管疾病风险标志物。APOC3基因胰岛素反应元件中的T-455C多态性会影响TG和apo C-III浓度。鱼类中含有的长链n-3多不饱和脂肪酸（PUFA）具有众所周知的降低apo C-III的特性。

方法

我们在848例接受冠状动脉造影的心脏病患者群体中，研究了APOC3基因变异与红细胞n-3 PUFA（脂肪酸饮食摄入量的合适标志物）之间对apo C-III浓度产生交互作用的可能性。

结果

在整个群体中，apo C-III浓度与红细胞总PUFA显著负相关，但仅考虑-455CC纯合个体时，这种相关性不显著。在整个群体以及-455TT和-455CT基因型的亚组中，apo C-III升高（即高于排除服用降脂药物个体后在整个群体中计算出的第75百分位数）的个体相对比例随着n-3 PUFA和二十二碳六烯酸浓度的增加而逐渐降低。在纯合-455CC亚组中观察到相反的情况，其中红细胞n-3 PUFA和二十二碳六烯酸浓度增加与apo C-III升高的个体比例较高相关。即使通过逻辑模型对可能的混杂变量[年龄、性别、体重指数、吸烟、冠状动脉疾病（CAD）/无CAD状态或使用降脂药物]进行调整后，基因型与n-3 PUFA之间的正式交互作用仍得到证实。