Grarup Niels, Andreasen Camilla H, Andersen Mette K, Albrechtsen Anders, Sandbaek Annelli, Lauritzen Torsten, Borch-Johnsen Knut, Jørgensen Torben, Schmitz Ole, Hansen Torben, Pedersen Oluf
Steno Diabetes Center, Niels Steensens Vej 1, Gentofte, Denmark.
J Clin Endocrinol Metab. 2008 Jun;93(6):2294-9. doi: 10.1210/jc.2007-2815. Epub 2008 Mar 25.
Hepatic lipase plays a pivotal role in the metabolism of high-density lipoprotein (HDL) and low-density lipoprotein by involvement in reverse cholesterol transport and the formation of atherogenic small dense low-density lipoprotein.
The objective was to investigate the impact of variants in LIPC on metabolic traits and type 2 diabetes in a large sample of Danes. Because behavioral factors influence hepatic lipase activity, we furthermore examined possible gene-environment interactions in the population-based Inter99 study.
The LIPC -250G>A (rs2070895) variant was genotyped in the Inter99 study (n = 6070), the Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen Detected Diabetes in Primary Care Denmark screening cohort of individuals with risk factors for undiagnosed type 2 diabetes (n = 8662), and in additional type 2 diabetic patients (n = 1,064) and glucose-tolerant control subjects (n = 360).
In the Inter99 study, the A allele of rs2070895 associated with a 0.057 mmol/liter [95% confidence interval (CI) 0.039-0.075] increase in fasting serum HDL-cholesterol (HDL-c) (P = 8 x 10(-10)) supported by association in the Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen Detected Diabetes in Primary Care study [0.038 mmol/liter per allele (95% CI 0.024-0.053); P = 2 x 10(-7)). The allelic effect on HDL-c was modulated by interaction with self-reported physical activity (P(interaction) = 0.002) because vigorous physically active homozygous A-allele carriers had a 0.30 mmol/liter (95% CI 0.22-0.37) increase in HDL-c compared with homozygous G-allele carriers.
We validate the association of LIPC promoter variation with fasting serum HDL-c and present data supporting an interaction with physical activity implying an increased effect on HDL-c in vigorous physically active subjects carrying the -250 A allele. This interaction may have potential implications for public health and disease prevention.
肝脂肪酶通过参与逆向胆固醇转运和致动脉粥样硬化的小而密低密度脂蛋白的形成，在高密度脂蛋白（HDL）和低密度脂蛋白的代谢中起关键作用。
本研究旨在调查丹麦人群中LIPC基因变异对代谢特征和2型糖尿病的影响。由于行为因素会影响肝脂肪酶活性，因此我们在基于人群的Inter99研究中进一步研究了可能的基因-环境相互作用。
在Inter99研究（n = 6070）、丹麦初级保健中筛查出的糖尿病患者强化治疗的英-丹-荷研究（n = 8662）以及另外的2型糖尿病患者（n = 1064）和糖耐量正常的对照者（n = 360）中，对LIPC -250G>A（rs2070895）变异进行基因分型。
在Inter99研究中，rs2070895的A等位基因与空腹血清高密度脂蛋白胆固醇（HDL-c）升高0.057 mmol/L [95%置信区间（CI）0.039 - 0.075]相关（P = 8×10⁻¹⁰），丹麦初级保健中筛查出的糖尿病患者强化治疗的英-丹-荷研究也支持这一关联[每个等位基因0.038 mmol/L（95% CI 0.024 - 0.053）；P = 2×10⁻⁷]。对HDL-c的等位基因效应受自我报告的身体活动的相互作用调节（P（相互作用）= 0.002），因为与纯合G等位基因携带者相比，剧烈身体活动的纯合A等位基因携带者的HDL-c升高0.30 mmol/L（95% CI 0.22 - 0.37）。
我们验证了LIPC启动子变异与空腹血清HDL-c的关联，并提供数据支持其与身体活动的相互作用，这意味着携带 -250 A等位基因且剧烈身体活动的个体对HDL-c的影响更大。这种相互作用可能对公共卫生和疾病预防具有潜在意义。
