Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, TX, USA.
Metabolism. 2010 Aug;59(8):1084-91. doi: 10.1016/j.metabol.2009.11.005. Epub 2009 Dec 31.
Insulin-induced gene 2 (INSIG2) plays an important role in the regulation of cholesterol and fatty acids synthesis. A polymorphism, rs7566605, located 10 kilobases upstream of the INSIG2 gene, was identified in a genomewide association study of obesity. We conducted an association study of 12 INSIG2 tag-single nucleotide polymorphisms with longitudinal measures of body size (body mass index and waist circumference) and lipid metabolism (plasma high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides levels). We investigated their interaction with age in 4304 Coronary Artery Risk Development in Young Adults participants (49.5% blacks, 50.5% whites) followed prospectively for 20 years. rs7566605 was not associated with variation in body size or lipid metabolism at any age in either racial group. However, rs1352083 and rs10185316 were associated with age-related decline in high-density lipoprotein cholesterol in whites (P = .0005 and .04, respectively). A similar trend was observed in blacks who consistently maintained a body mass index less than 25 kg/m(2) over the study period. These data support a role of INSIG2 sequence variation in the regulation of cholesterol metabolism.
胰岛素诱导基因 2（INSIG2）在胆固醇和脂肪酸合成的调节中起着重要作用。在肥胖的全基因组关联研究中，发现了 INSIG2 基因上游 10 千碱基处的一个多态性 rs7566605。我们对 12 个 INSIG2 标签单核苷酸多态性与身体大小（体重指数和腰围）和脂质代谢（血浆高密度脂蛋白胆固醇、低密度脂蛋白胆固醇和甘油三酯水平）的纵向测量进行了关联研究。我们在 4304 名冠状动脉风险发展中的年轻人参与者（49.5%的黑人，50.5%的白人）中研究了它们与年龄的相互作用，这些参与者前瞻性地随访了 20 年。在任何年龄、任何种族组中，rs7566605 与身体大小或脂质代谢的变化均无关。然而，rs1352083 和 rs10185316 与白人高密度脂蛋白胆固醇的年龄相关性下降有关（分别为 P =.0005 和.04）。在研究期间一直保持体重指数低于 25 kg/m(2)的黑人中，也观察到了类似的趋势。这些数据支持 INSIG2 序列变异在胆固醇代谢调节中的作用。
