Institute of Metabolic Science, MRC Epidemiology Unit, Cambridge, UK.
Obesity (Silver Spring). 2010 Oct;18(10):1975-80. doi: 10.1038/oby.2010.13. Epub 2010 Feb 4.
Phosphoenolpyruvate carboxykinase-1 (PCK1) is the rate-limiting enzyme in the hepatic gluconeogenic pathway. Studies have shown that overexpression of Pck1 in mice results in obesity-related traits and higher levels of physical activity (PA). Therefore, our aims were to investigate whether common genetic variation in the PCK1 gene influences obesity-related traits, PA, and fitness, and to examine whether PA and fitness attenuate the influence of the PCK1 polymorphisms on obesity in children. Analyses were undertaken on data from Danish and Estonian children (958 boys and 1,104 girls) from the European Youth Heart Study (EYHS), a school-based, cross-sectional study of children (mean ± s.d. age: 9.6 ± 0.4 years) and adolescents (15.5 ± 0.5 years). We genotyped eight polymorphisms that captured the common genetic variations in the PCK1 gene. The association between the PCK1 polymorphisms and BMI, waist circumference (WC), sum of four skinfolds, PA, and fitness was tested using an additive model adjusted for age, age-group, gender, maturity, and country. Interactions were tested by including interaction terms in the model. None of the polymorphisms were significantly associated with BMI, WC, sum of four skinfolds, PA, and fitness, and also with the risk of being overweight or obese (P > 0.05). The interactions between the polymorphisms and age-group, gender, PA, and fitness were not statistically significant. This is the first study to comprehensively examine the association of PCK1 polymorphisms with obesity, PA, and fitness. Despite strong evidence from animal studies, our study in the EYHS cohort failed to identify an association of PCK1 polymorphisms with obesity, PA, and fitness.
磷酸烯醇式丙酮酸羧激酶 1（PCK1）是肝脏糖异生途径中的限速酶。研究表明，Pck1 在小鼠中的过度表达会导致肥胖相关特征和更高水平的体力活动（PA）。因此，我们的目的是研究 PCK1 基因中的常见遗传变异是否会影响肥胖相关特征、PA 和适应性，以及检查 PA 和适应性是否会减弱 PCK1 多态性对儿童肥胖的影响。对来自丹麦和爱沙尼亚儿童（958 名男孩和 1104 名女孩）的欧洲青年心脏研究（EYHS）数据进行了分析，该研究是一项基于学校的儿童（平均±标准差年龄：9.6±0.4 岁）和青少年（15.5±0.5 岁）的横断面研究。我们对 8 个多态性进行了基因分型，这些多态性捕获了 PCK1 基因中的常见遗传变异。使用加性模型调整年龄、年龄组、性别、成熟度和国家，测试了 PCK1 多态性与 BMI、腰围（WC）、四个皮褶厚度之和、PA 和适应性之间的关系。通过在模型中包含交互项来测试交互作用。没有一个多态性与 BMI、WC、四个皮褶厚度之和、PA 和适应性以及超重或肥胖的风险显著相关（P＞0.05）。多态性与年龄组、性别、PA 和适应性之间的交互作用没有统计学意义。这是第一项全面研究 PCK1 多态性与肥胖、PA 和适应性之间关系的研究。尽管动物研究提供了强有力的证据，但我们在 EYHS 队列中的研究未能确定 PCK1 多态性与肥胖、PA 和适应性之间的关联。
