Apolipoprotein E gene polymorphism and risk of type 2 diabetes and cardiovascular disease.
Apolipoprotein E gene polymorphism and risk of type 2 diabetes and cardiovascular disease.
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DOI：
10.1186/s12933-016-0329-1
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发表时间：
2016-01-22
影响因子：
9.3
通讯作者：
Mohammed AM
中科院分区：
文献类型：
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作者：
El-Lebedy D;Raslan HM;Mohammed AM
脂蛋白相关机制与糖尿病患者心血管系统的损害有关。载脂蛋白E基因是研究最多的候选基因之一，其影响脂蛋白的清除，从而影响我们体内的脂质分布，并且最近被报道与T2 DM和CAD相关。本研究旨在探讨载脂蛋白E基因多态性与2型糖尿病和心血管疾病的关系及其对血脂谱的影响。我们的研究在284名受试者中进行，分为100名T2 DM患者，100名T2 DM合并CVD患者和84名正常对照者。使用TaqMan® SNP基因分型测定通过实时PCR对ApoE基因多态性进行基因分型。ApoE基因型以E3/E3型最常见。E3/E4基因型和ε4等位基因频率在2型糖尿病组和心血管病组均高于对照组，但仅心血管病组差异有统计学意义（p = 0.004和0.007）。携带E3/E4基因型的糖尿病患者发生CVD的风险增加2.4倍（95%CI 1.14-5.19，P = 0.02），携带ε4等位基因的糖尿病患者发生CVD的风险增加2.23倍（95%CI 1.09-4.59，P = 0.02）。在调整其他已确定的危险因素后，E3/E4基因型是CVD的独立危险因素（OR = 2.3，p = 0.009），但不适用于T2 DM（OR = 1.7，p = 0.28），而ε4等位基因是2型糖尿病和2型糖尿病的独立危险因素（OR = 2.2，p = 0.04）和CVD（OR = 3.0，p = 0.018），T2 DM患者发生CVD的风险增加5.9倍（p = 0.019）。E3/E4基因型在所有组中均与显著较高的TC和非HDL-C水平相关，在T2 DM和CVD患者中均与显著较高的LDL-C水平相关。ApoE基因多态性与心血管疾病相关，并影响血脂谱。ε4等位基因是T2 DM和CVD的独立危险因素。进一步的遗传学研究将增加T2 DM中传统心血管危险因素以外的信息，并确定风险基因型，这将有助于早期预测和识别风险患者。
Lipoprotein-related mechanisms have been associated with damage to the cardiovascular system in diabetic patients. Apolipoprotein E gene which affects the clearance of lipoproteins and consequently the lipid profile in our body is one of the most studied candidate genes and recently has been reported to be associated with T2DM and CAD. In this work, we studied the association of apoE gene polymorphism with T2DM and CVD and its effect on plasma lipids profile. Our study was conducted on 284 subjects categorized into 100 patients with T2DM, 100 patients with T2DM complicated with CVD and 84 normal control subjects. ApoE gene polymorphism was genotyped by real-time PCR using TaqMan® SNP Genotyping Assay. ApoE E3/E3 genotype was the most common in our subjects. The frequencies of E3/E4 genotype and ε4 allele were increased in both T2DM patients and CVD patients as compared with controls, but were significant only in CVD patients (p = 0.004 and 0.007, respectively). Diabetic patients who carried E3/E4 genotype were at 2.4-fold increased risk to develop CVD (95 % CI 1.14–5.19, P = 0.02) and the ε4 allele associated with 2.23-fold higher CVD risk (95 % CI 1.09–4.59, P = 0.02). After adjustment for other established risk factors, E3/E4 genotype was an independent risk factor for CVD (OR = 2.3, p = 0.009) but not for T2DM (OR = 1.7, p = 0.28), while ε4 allele was an independent risk factor for both T2DM (OR = 2.2, p = 0.04) and CVD (OR = 3.0, p = 0.018) with 5.9-fold increased risk to develop CVD in T2DM patients (p = 0.019). E3/E4 genotype associated with significantly higher levels of TC and non HDL-C in all groups and with significantly higher levels of LDL-C in both T2DM and CVD patients. ApoE gene polymorphisms associate with CVD and affect the lipid profile. The ε4 allele is an independent risk factor for both T2DM and CVD. Further genetic studies to add information beyond the traditional cardiovascular risk factors in T2DM and to identify risk genotypes will help in early prediction and identification of at risk patients.