Type 2 diabetes mellitus interacts with obesity and common variations in PLTP to affect plasma phospholipid transfer protein activity
Type 2 diabetes mellitus interacts with obesity and common variations in PLTP to affect plasma phospholipid transfer protein activity
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DOI：
10.1111/j.1365-2796.2011.02465.x
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发表时间：
2012-05-01
影响因子：
11.1
通讯作者：
Dallinga-Thie, G. M.
中科院分区：
文献类型：
--
作者：
Dullaart, R. P. F.;Vergeer, M.;Dallinga-Thie, G. M.
Dullaart RPF，Vergeer M，de弗里斯R，Kappelle PJWH，Dallinga-Thie GM（格罗宁根大学医学中心，格罗宁根大学，格罗宁根;阿姆斯特丹学术医学中心，阿姆斯特丹;荷兰）。2型糖尿病与肥胖和PLTP的常见变异相互作用，影响血浆磷脂转移蛋白活性。J Intern Med 2012; 271：490498.背景磷脂转移蛋白（PLTP）是一种新兴的心脏代谢危险标志物，在高密度脂蛋白（HDL）和甘油三酯代谢中起重要作用。2型糖尿病患者血浆PLTP活性升高，而葡萄糖可能在体外调节PLTP基因转录。有趣的是，最近已经确定了预测心血管疾病的常见PLTP变异。我们研究了糖尿病状态是否能够放大肥胖和PLTP基因变异与循环PLTP水平之间的关系。主题和方法。血浆PLTP活性（使用磷脂囊泡HDL系统），PLTP基因评分[基于两个标记多态性（rs378114和rs60- 65904）的PLTP活性降低等位基因的数量]和腰围在两个荷兰队列中测定，包括237例2型糖尿病患者和78例对照受试者。结果糖尿病患者更肥胖（腰围增加的患病率P < 0.001），血浆PLTP活性高13%（P < 0.001）。PLTP基因评分在糖尿病组和对照组无差异（P = 0.40）。PLTP活性在腰围增大的糖尿病患者中最高，而在腰围正常的对照组中最低（P < 0.001）。多元线性回归分析显示糖尿病状态和腰围对PLTP活性的正交互作用（β = 0.200，P = 0.005）。此外，糖尿病状态（β =-0.485，P = 0.046）或HbA 1c（β =-0.240，P = 0.035）与PLTP基因评分相互作用，影响PLTP活性。结论. 2型糖尿病和腰围增大相互作用影响血浆PLTP活性。糖尿病还可能放大血浆PLTP活性与常见PLTP基因变异之间的关联。我们的研究结果支持糖尿病易感性和糖尿病基因相互作用控制血浆PLTP活性的假说。
Dullaart RPF, Vergeer M, de Vries R, Kappelle PJWH, Dallinga-Thie GM (University Medical Center Groningen, University of Groningen, Groningen; and Academic Medical Center Amsterdam, Amsterdam; The Netherlands). Type 2 diabetes mellitus interacts with obesity and common variations in PLTP to affect plasma phospholipid transfer protein activity. J Intern Med 2012; 271: 490498. Background. Phospholipid transfer protein (PLTP) is an emerging cardiometabolic risk marker that is important in high-density lipoprotein (HDL) and triglyceride metabolism. Plasma PLTP activity is elevated in type 2 diabetes mellitus, whereas glucose may regulate PLTP gene transcription in vitro. Of interest, common PLTP variations that predict cardiovascular disease have been identified recently. We investigated whether the diabetic state is able to amplify relationships between obesity and PLTP gene variations with circulating PLTP levels. Subjects and methods. Plasma PLTP activity (using a phospholipid vesiclesHDL system), PLTP gene score [number of PLTP activity-decreasing alleles based on two tagging polymorphisms (rs378114 and rs60- 65904)] and waist circumference were determined in two Dutch cohorts comprising 237 patients with type 2 diabetes and 78 control subjects. Results. Patients with diabetes were more obese (P < 0.001 for prevalence of increased waist circumference) and had 13% higher plasma PLTP activity (P < 0.001). PLTP gene score was not different in diabetic and control subjects (P = 0.40). PLTP activity was highest in patients with diabetes with an enlarged waist and lowest in control subjects with a normal waist circumference (P < 0.001). Multiple linear regression analysis revealed a positive interaction between diabetes status and waist circumference on PLTP activity (beta = 0.200, P = 0.005). Furthermore, diabetes status (beta = -0.485, P = 0.046) or HbA1c (beta = -0.240, P = 0.035) interacted with PLTP gene score to affect PLTP activity. Conclusions. Type 2 diabetes and enlarged waist circumference interact to impact on plasma PLTP activity. Diabetes may also amplify the association between plasma PLTP activity and common PLTP gene variations. Our findings support the hypothesis that diabetesenvironment and diabetesgene interactions govern plasma PLTP activity.