Apolipoprotein E gene polymorphism: effects on plasma lipids and risk of type 2 diabetes and coronary artery disease.
Apolipoprotein E gene polymorphism: effects on plasma lipids and risk of type 2 diabetes and coronary artery disease.
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DOI：
10.1186/1475-2840-11-36
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发表时间：
2012-04-23
影响因子：
9.3
通讯作者：
Sriratanasathavorn C
中科院分区：
文献类型：
--
作者：
Chaudhary R;Likidlilid A;Peerapatdit T;Tresukosol D;Srisuma S;Ratanamaneechat S;Sriratanasathavorn C
载脂蛋白E（apoE）基因多态性是影响血脂水平的最常见的基因，其与冠心病的相关性在过去的十年中得到了广泛的研究。然而，目前尚不清楚apoE基因多态性是否也与2型糖尿病（T2 DM）的风险增加。本研究的知识可能为T2 DM和CAD的发生和进展提供一级预防。因此，本研究旨在探讨载脂蛋白E基因多态性与2型糖尿病合并或不合并冠心病的关系及其在脂代谢中的作用。共对451例样本进行了病例对照研究，包括149例正常对照者、155例T2 DM患者和147例T2 DM合并CAD患者。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法检测apoE基因多态性。采用单变量和多变量logistic回归分析确定T2 DM和CAD的可能风险。E3/E4基因型频率仅在T2 DM合并CAD组中显著增加（p = 0.0004），而ε4等位基因在T2 DM（p = 0.047）和T2 DM合并CAD组（p = 0.009）中均显著高于对照组。E3/E4基因型也是冠心病的独立危险因素，调整后OR为2.52（95%CI 1.28-4.97，p = 0.008）。携带ε4等位基因个体的独立预测因子仍然与CAD（校正OR 2.32，95%CI 1.17-4.61，p = 0.016）和T2 DM（校正OR 2.04，95%CI 1.07-3.86，p = 0.029）显著相关。在同时检查E3/E4基因型与肥胖或吸烟的联合相关性后，T2 DM的风险增加约5倍（校正OR 4.93，95%CI 1.74-13.98，p = 0.003），CAD的风险增加约10倍（校正OR 10.48，95%CI 3.56-30.79，p < 0.0001）。以E3/E3为参考基因型，以E4基因型为对照基因型，比较apoE基因型与血脂水平的关系。E4基因型的HDL-C较低，VLDL-C和TG较高，而其他血脂水平无显著差异。这些结果表明，ε4等位基因对血脂谱有影响，并且与伴或不伴CAD的T2 DM的发展相关，此外，它增加了肥胖和/或吸烟受试者的风险，这些条件与高氧化应激相关。
The most common apolipoprotein E (apoE) gene polymorphism has been found to influence plasma lipid concentration and its correlation with coronary artery disease (CAD) has been extensively investigated in the last decade. It is, however, unclear whether apoE gene polymorphism is also associated with increased risk of type 2 diabetes mellitus (T2DM). The knowledge of this study may provide the primary prevention for T2DM and CAD development before its initiation and progression. Therefore, this study was carried out to determine the association between apoE gene polymorphism and T2DM with and without CAD and its role in lipid metabolism. The case-control study was carried out on a total of 451 samples including 149 normal control subjects, 155 subjects with T2DM, and 147 subjects with T2DM complicated with CAD. The apoE gene polymorphism was tested by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Univariable and multivariable logistic regression analyses were used to identify the possible risks of T2DM and CAD. A significantly increased frequency of E3/E4 genotype was observed only in T2DM with CAD group (p = 0.0004), whereas the ε4 allele was significantly higher in both T2DM (p = 0.047) and T2DM with CAD (p = 0.009) as compared with controls. E3/E4 genotype was also the independent risk in developing CAD after adjusting with established risk factors with adjusted odds ratio (OR) 2.52 (95%CI 1.28-4.97, p = 0.008). The independent predictor of individuals carrying ε4 allele still remained significantly associated with both CAD (adjusted OR 2.32, 95%CI 1.17-4.61, p = 0.016) and T2DM (adjusted OR 2.04, 95%CI 1.07-3.86, p = 0.029). After simultaneously examining the joint association of E3/E4 genotype combined with either obesity or smoking the risk increased to approximately 5-fold in T2DM (adjusted OR 4.93, 95%CI 1.74-13.98, p = 0.003) and 10-fold in CAD (adjusted OR 10.48, 95%CI 3.56-30.79, p < 0.0001). The association between apoE genotypes on plasma lipid levels was compared between E3/E3 as a reference and E4-bearing genotypes. E4-bearing genotypes showed lower HDL-C and higher VLDL-C and TG, whereas other values of plasma lipid concentrations showed no significant difference. These results indicate that ε4 allele has influence on lipid profiles and is associated with the development of both T2DM with and without CAD, and furthermore, it increased the risk among the subjects with obesity and/or smoking, the conditions associated with high oxidative stress.
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影响因子：
5.3
作者：
Gómez-Coronado, D;Alvarez, JJ;Lasunción, MA
通讯作者：
Lasunción, MA
影响因子：
9.3
作者：
Hermans MP;Sacks FM;Ahn SA;Rousseau MF
通讯作者：
Rousseau MF
影响因子：
2.8
作者：
Corbo, RM;Vilardo, T;Scacchi, R
通讯作者：
Scacchi, R
影响因子：
2.8
作者：
EICHNER, JE;KULLER, LH;NEATON, JD
通讯作者：
NEATON, JD
影响因子：
5
作者：
Attila, G;Acartürk, E;Kayrin, L
通讯作者：
Kayrin, L