Tsuzaki Kokoro, Kotani Kazuhiko, Fujiwara Shinji, Sano Yoshiko, Matsuoka Yukiyo, Domichi Masayuki, Hamada Taku, Shimatsu Akira, Sakane Naoki
Department of Preventive Medicine, Clinical Research Institute for Endocrine and Metabolic Disease, National Hospital Organization Kyoto Medical Center, Kyoto, Japan.
Metabolism. 2007 Dec;56(12):1689-93. doi: 10.1016/j.metabol.2007.07.012.
The presence of small dense low-density lipoprotein (sdLDL) is closely associated with an increased risk of developing coronary artery disease. The Trp64Arg polymorphism of the beta(3)-adrenergic receptor (beta(3)-AR) gene is a genetic marker for obesity-related traits. However, any possible association between this polymorphism and sdLDL profiles is unclear. The objective of this study is to investigate the effects of the polymorphism of the beta(3)-AR gene on LDL particle size and sdLDL in a rural Japanese population. Among 277 subjects, body mass index, blood pressure, fasting serum insulin levels, and insulin resistance index (fasting glucose x fasting insulin/405) were determined. The polymorphism of the beta(3)-AR gene was assessed by polymerase chain reaction-restriction fragment length polymorphism using buccal samples. Low-density lipoprotein particle size and sdLDL were measured with the electrophoretic separation of lipoproteins on the LipoPrint System (Quantimetrix, Redondo Beach, CA). The frequency of the beta(3)-AR allele was 0.19. In Arg carriers (Trp/Arg or Arg/Arg), the mean value of LDL particle size was smaller than that of non-Arg carriers (Trp/Trp) (P < .05). The area percentage of sdLDL was higher in Arg carriers (P < .05) than in non-Arg carriers. A multiple regression analysis showed that the area percentage of sdLDL was correlated with the polymorphism of the beta(3)-AR gene (P < .05), independently of age, sex, body mass index, smoking, and insulin resistance index. The present findings suggest that the beta(3)-AR gene polymorphism plays a role in the genetic predisposition to increased sdLDL, independently of insulin resistance.
小而密的低密度脂蛋白（sdLDL）的存在与冠状动脉疾病发生风险的增加密切相关。β(3)-肾上腺素能受体（β(3)-AR）基因的色氨酸64精氨酸多态性是肥胖相关性状的一个遗传标记。然而，这种多态性与sdLDL谱之间的任何可能关联尚不清楚。本研究的目的是调查β(3)-AR基因多态性对日本农村人群低密度脂蛋白颗粒大小和sdLDL的影响。在277名受试者中，测定了体重指数、血压、空腹血清胰岛素水平和胰岛素抵抗指数（空腹血糖×空腹胰岛素/405）。使用颊部样本通过聚合酶链反应-限制性片段长度多态性来评估β(3)-AR基因的多态性。通过LipoPrint系统（Quantimetrix，加利福尼亚州雷东多海滩）上脂蛋白的电泳分离来测量低密度脂蛋白颗粒大小和sdLDL。β(3)-AR等位基因的频率为0.19。在精氨酸携带者（Trp/Arg或Arg/Arg）中，低密度脂蛋白颗粒大小的平均值低于非精氨酸携带者（Trp/Trp）（P < 0.05）。精氨酸携带者中sdLDL的面积百分比高于非精氨酸携带者（P < 0.05）。多元回归分析表明，sdLDL的面积百分比与β(3)-AR基因的多态性相关（P < 0.05），独立于年龄、性别、体重指数、吸烟和胰岛素抵抗指数。目前的研究结果表明，β(3)-AR基因多态性在sdLDL增加的遗传易感性中起作用，独立于胰岛素抵抗。
