Adipocyte and Fat Biology Laboratory (AdipoFat), Unidad de Investigación Traslacional, Hospital Universitario Miguel Servet, Instituto Aragonés de Ciencias de la Salud (IACS), Zaragoza, Spain; Instituto de Investigación Sanitaria (IIS) Aragón, Zaragoza, Spain.
Instituto de Investigación Sanitaria (IIS) Aragón, Zaragoza, Spain; Unidad de Prevención Cardiovascular, Instituto Aragonés de Ciencias de la Salud (IACS), Zaragoza, Spain.
Atherosclerosis. 2016 Feb;245:35-42. doi: 10.1016/j.atherosclerosis.2015.11.029. Epub 2015 Dec 2.
The human Apolipoprotein E (APOE) gene is polymorphic. The APOE*4 allele is a risk factor for cardiovascular disease and could contribute to the development of the metabolic syndrome (MetS) as it may affect all MetS components. We hypothesize that the common APOE4 polymorphism differentially regulates MetS risk and that this association might be modulated by body fatness.
METHODS & RESULTS: We used body mass index (BMI) as surrogate of fatness and cross-sectionally studied the prevalence of MetS in 4408 middle-aged men of the Aragon Workers Health Study (AWHS). Our analysis revealed i) a gene dose-dependent association between APOE4 allele and increased risk for MetS, ii) this association primarily derived from the overweight subjects. For these individuals, the MetS risk was higher in APOE4 carriers than in non-carriers (Odds Ratio = 1.31; 95% CI, 1.03-1.67). Additionally, we examined 3908 healthy young individuals from the Coronary Artery Risk Development in Young Adults (CARDIA) cohort, followed-up for 25 years. Compared with APOE4 non-carriers, APOE4 presence significantly increased the risk of developing MetS (Hazard Ratio, 1.12; 95% CI, 1.00-1.26). Again, an interplay between APOE4 and the longitudinal development of fatness towards the onset of MetS occurred throughout the study. For individuals with BMI gain below the median, the cumulative onset rate of MetS was significantly higher in APOE4 carriers than in the non-carriers (HR, 1.29; 95% CI, 1.07-1.55).
Carrying APOE*4 alleles increases MetS in a dose-dependent manner, characterizing individual's APOE genotype might help identify at-risk subjects for preventive intervention.
人类载脂蛋白 E（APOE）基因多态性。APOE*4 等位基因是心血管疾病的危险因素，可能会影响所有代谢综合征（MetS）的组分，从而导致代谢综合征的发生。我们假设常见的 APOE4 多态性会对代谢综合征的风险产生差异调节，而这种关联可能会受到体脂含量的调节。
我们使用体重指数（BMI）作为体脂的替代指标，对 4408 名中年男性的阿拉贡工人健康研究（AWHS）进行了横断面研究，分析了代谢综合征的患病率。我们的分析显示，APOE4 等位基因与代谢综合征的风险呈剂量依赖性相关，ii）这种关联主要来源于超重人群。对于这些个体，APOE4 携带者发生代谢综合征的风险高于非携带者（比值比=1.31；95%置信区间，1.03-1.67）。此外，我们对冠状动脉风险发展在年轻人（CARDIA）队列中 3908 名健康的年轻人进行了研究，随访 25 年。与 APOE4 非携带者相比，APOE4 存在显著增加了代谢综合征的发病风险（风险比，1.12；95%置信区间，1.00-1.26）。同样，APOE4 与肥胖的纵向发展之间存在相互作用，在整个研究中，这种相互作用会导致代谢综合征的发生。对于 BMI 增长低于中位数的个体，APOE4 携带者的代谢综合征累积发病风险显著高于非携带者（HR，1.29；95%置信区间，1.07-1.55）。
携带 APOE*4 等位基因以剂量依赖性方式增加代谢综合征的发病风险，确定个体的 APOE 基因型可能有助于识别高危患者，以便进行预防性干预。
