APOE基因多态性与糖尿病及心血管代谢危险因素的关联以及APOE基因型在抗糖尿病治疗反应中的作用：来自南亚人群AIDHS/SDS的结果
Association of APOE polymorphisms with diabetes and cardiometabolic risk factors and the role of APOE genotypes in response to anti-diabetic therapy: results from the AIDHS/SDS on a South Asian population.
作者信息
Sapkota Bishwa, Subramanian Anuradha, Priamvada Gargi, Finely Hadley, Blackett Piers R, Aston Christopher E, Sanghera Dharambir K
机构信息
Department of Pediatrics, Section of Genetics, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Department of Pediatrics, Section of Endocrinology, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
出版信息
J Diabetes Complications. 2015 Nov-Dec;29(8):1191-7. doi: 10.1016/j.jdiacomp.2015.07.025. Epub 2015 Aug 1.
BACKGROUND AND OBJECTIVES
Apolipoprotein E (APOE) gene polymorphisms have been examined extensively in multiple global populations particularly due to their crucial role in lipid metabolism and cardiovascular disease. However, the overall contribution of APOE polymorphisms in type 2 diabetes (T2D) and coronary artery disease (CAD) in South Asians is still under-investigated. The objectives of this investigation were: 1) to evaluate the distribution of APOE polymorphisms in a large diabetic case-control sample from South Asia, 2) to examine the impact of APOE polymorphisms on quantitative risk factors of T2D and CAD, and 3) to explore the contribution of APOE genotypes in the response to anti-diabetic therapy.
SUBJECTS AND METHODS
A total of 3564 individuals (1956 T2D cases and 1608 controls) used in this study were part of the Asian Indian Diabetic Heart Study/Sikh Diabetes Study (AIDHS/SDS). We assessed the association of APOE polymorphisms with T2D, CAD and cardiometabolic traits using logistic and linear regression analysis.
RESULTS AND CONCLUSIONS
No significant differences in the distribution of APOE genotypes were observed between T2D and CAD cases and controls. The APOE4 genotype carriers had moderately higher diastolic blood pressure (BP) (p=0.022), and lower HDL-cholesterol (p=0.026) compared to E4 non-carriers. Overall, the APOE genotype was not a significant predictor of cardiometabolic disease in this population. Further stratification of data from diabetic patients by APOE genotypes and anti-hyperglycemic agents revealed a significant (~23%) decrease in 2-hour glucose (p=0.004) and ~7% decrease in systolic BP (p<0.001) among APOE4 carriers compared to non-carriers on metformin and sulphonylurea (SU) combination therapy, and no such differences were seen in patients on other agents. Our preliminary findings point to the need for evaluating population-specific genetic variation and its interactions with therapeutic effects.
背景与目的
载脂蛋白E（APOE）基因多态性在多个全球人群中得到了广泛研究，特别是因其在脂质代谢和心血管疾病中的关键作用。然而，APOE基因多态性在南亚2型糖尿病（T2D）和冠状动脉疾病（CAD）中的总体贡献仍研究不足。本研究的目的是：1）评估APOE基因多态性在来自南亚的大型糖尿病病例对照样本中的分布；2）研究APOE基因多态性对T2D和CAD定量危险因素的影响；3）探讨APOE基因型在抗糖尿病治疗反应中的作用。
对象与方法
本研究共纳入3564名个体（1956例T2D患者和1608名对照），他们是亚洲印度糖尿病心脏研究/锡克糖尿病研究（AIDHS/SDS）的一部分。我们使用逻辑回归和线性回归分析评估APOE基因多态性与T2D、CAD和心脏代谢特征之间的关联。
结果与结论
在T2D和CAD病例与对照之间，未观察到APOE基因型分布的显著差异。与非E4携带者相比，APOE4基因型携带者的舒张压（BP）略高（p=0.022），高密度脂蛋白胆固醇略低（p=0.026）。总体而言，APOE基因型不是该人群心脏代谢疾病的显著预测指标。按APOE基因型和抗高血糖药物对糖尿病患者数据进行进一步分层后发现，与接受二甲双胍和磺脲类药物（SU）联合治疗的非携带者相比，APOE4携带者的2小时血糖显著降低（约23%，p=0.004），收缩压降低约7%（p<0.001），而使用其他药物的患者未观察到此类差异。我们的初步研究结果表明，有必要评估特定人群的基因变异及其与治疗效果的相互作用。
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