Ukkola O, Pérusse L, Weisnagel S J, Bergeron J, Després J P, Rao D C, Bouchard C
Pennington Biomedical Research Center, Baton Rouge, LA, USA.
Metabolism. 2001 Feb;50(2):246-52. doi: 10.1053/meta.2001.18572.
The aim of the study was to investigate the possible interactions among the glucocorticoid receptor (GRL), lipoprotein lipase (LPL), and adrenergic receptor (ADR) genes on plasma insulin and lipid levels. The study was cross-sectional and based on 742 individuals from phase 2 of the Quebec Family Study (QFS) cohort. Gene markers were identified by Southern blot analysis or polymerase chain reaction (PCR). Plasma glucose and insulin in the fasted state and during an oral glucose tolerance test (OGTT) were determined and insulin and glucose areas were computed. Triglyceride (TG) and cholesterol concentrations in plasma and lipoprotein fractions were determined enzymatically. The results show that GRL and LPL variants had independent effects on plasma high-density lipoprotein cholesterol (HDL-C) and two beta2-ADR variants were related to total cholesterol concentrations. The alpha2-ADR gene Dral polymorphism was the only variant that had an independent effect on the plasma insulin area. Gene-gene interaction effects were found between GRL and alpha2-ADR genes for low-density lipoprotein cholesterol ([LDL-C] P = .013) and between GRL and LPL genes for HDL-C (P = .045). Higher-order interaction effects involving GRL, LPL, and ADR markers were observed for the plasma insulin area (P = .001 to .025) but not the glucose area. After correction for multiple tests, the findings remained essentially unchanged for the insulin area but became nonsignificant for the lipid phenotypes. In conclusion, multiple interactions among GRL, LPL, and ADR gene markers contribute to insulin metabolism and perhaps to lipid levels, while no significant effect is found for each gene separately. The LPL locus appears to determine the pattern of interactions with ADR and GRL loci. These results suggest that gene-gene interaction effects could play a role in the etiology of risk factors for common chronic diseases.
本研究的目的是调查糖皮质激素受体（GRL）、脂蛋白脂肪酶（LPL）和肾上腺素能受体（ADR）基因之间可能存在的相互作用对血浆胰岛素和脂质水平的影响。该研究为横断面研究，基于魁北克家庭研究（QFS）队列第2阶段的742名个体。通过Southern印迹分析或聚合酶链反应（PCR）鉴定基因标记。测定空腹状态下以及口服葡萄糖耐量试验（OGTT）期间的血浆葡萄糖和胰岛素水平，并计算胰岛素和葡萄糖曲线下面积。采用酶法测定血浆和脂蛋白组分中的甘油三酯（TG）和胆固醇浓度。结果显示，GRL和LPL变异对血浆高密度脂蛋白胆固醇（HDL-C）有独立影响，两种β2-ADR变异与总胆固醇浓度相关。α2-ADR基因Dral多态性是唯一对血浆胰岛素曲线下面积有独立影响的变异。发现GRL与α2-ADR基因之间对低密度脂蛋白胆固醇（[LDL-C] P = 0.013）存在基因-基因相互作用效应，GRL与LPL基因之间对HDL-C存在基因-基因相互作用效应（P = 0.045）。观察到涉及GRL、LPL和ADR标记的高阶相互作用效应作用于血浆胰岛素曲线下面积（P = 0.001至0.025），但对葡萄糖曲线下面积无影响。在进行多重检验校正后，胰岛素曲线下面积的研究结果基本保持不变，但脂质表型的结果变得无统计学意义。总之，GRL、LPL和ADR基因标记之间的多重相互作用有助于胰岛素代谢，可能也有助于脂质水平，而单个基因未发现显著影响。LPL基因座似乎决定了与ADR和GRL基因座的相互作用模式。这些结果表明基因-基因相互作用效应可能在常见慢性病危险因素的病因学中起作用。
