载脂蛋白ε4和ε2等位基因的存在会增加2型糖尿病患者患冠状动脉疾病的风险。

The presence of apolipoprotein epsilon4 and epsilon2 alleles augments the risk of coronary artery disease in type 2 diabetic patients.

作者信息

Vaisi-Raygani Asad, Rahimi Zohreh, Nomani Hamid, Tavilani Haidar, Pourmotabbed Tayebeh

机构信息

Department of Clinical Biochemistry, Kermanshah University of Medical Sciences, Kermanshah, Iran.

出版信息

Clin Biochem. 2007 Oct;40(15):1150-6. doi: 10.1016/j.clinbiochem.2007.06.010. Epub 2007 Jul 6.

DOI:10.1016/j.clinbiochem.2007.06.010

PMID:17689519

Abstract

OBJECTIVE

It has been suggested that there is a relationship between apolipoprotein E polymorphism and the severity of coronary artery disease in type II diabetes mellitus (T2DM). The current study specifically aimed to examine whether APOE polymorphism in association with serum lipids-lipoproteins level is a risk factor for developing coronary artery disease (CAD) in diabetic patients living in western of Iran.

METHODS

The APOE genotypes were detected by PCR-RFLP in 152 angiographically documented diabetic CAD patients, 262 non-diabetic (ND) individuals with CAD and 300 unrelated controls (normal coronary artery cases without diabetes) and serum lipid level was measured enzymatically.

RESULTS

The APOE-epsilon4 and epsilon2 allele frequencies were significantly higher in the CAD/T2DM and CAD/ND patients than in the control group (p<0.001). Our study demonstrated a significant association between APOE polymorphism and the level of plasma lipids with CAD/T2DM (p=0.001) and CAD/ND (p=0.026) patients. The CAD subjects with T2DM and ND patients carrying APOE-epsilon4 allele had lower plasma HDL-C level (p<0.001), (p=0.008) but had higher plasma LDL-C (p=0.01), total cholesterol (p=0.002), (p=0.03) and TG (p<0.001), (p=0.042) than that of the APOE-epsilon3 carriers, respectively. However, carriers of APOE-epsilon2 had significantly higher levels of plasma TG only. OR of APOE-epsilon4 and epsilon2 alleles in CAD/T2DM and CAD/ND patients were found to be 2.98 (p=0.001),1.86 (p=0.001), 2 (p=0.001), and 1.65 (p=0.001), respectively.

CONCLUSIONS

The major finding of the present case-control study is that T2DM patients carrying APOE-epsilon2 and epsilon4 alleles have a higher risk of developing CAD than ND patients in the western population of Iran, with APOE-epsilon4 being more closely associated with CAD than the APOE-epsilon2 allele. These results indicated that carriers of APOE-epsilon4 allele have a distinct plasma lipids profile and carrier of this allele with low levels of HDL-C and with high levels of LDL-C may be susceptible to CAD and myocardial infarction specially in diabetic patients. This suggests that a therapeutic modality should be considered for these patients.

摘要

目的

有人提出载脂蛋白E多态性与II型糖尿病（T2DM）患者冠状动脉疾病的严重程度之间存在关联。本研究的具体目的是检验在伊朗西部生活的糖尿病患者中，APOE多态性与血脂-脂蛋白水平相关联是否是发生冠状动脉疾病（CAD）的危险因素。

方法

采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法检测152例经血管造影证实的糖尿病CAD患者、262例非糖尿病（ND）CAD患者和300例无亲缘关系的对照者（无糖尿病的正常冠状动脉病例）的APOE基因型，并采用酶法测定血脂水平。

结果

CAD/T2DM组和CAD/ND组患者的APOE-ε4和ε2等位基因频率显著高于对照组（p<0.001）。我们的研究表明，APOE多态性与CAD/T2DM组（p=0.001）和CAD/ND组（p=0.026）患者的血脂水平之间存在显著关联。携带APOE-ε4等位基因的T2DM CAD患者和ND患者的血浆高密度脂蛋白胆固醇（HDL-C）水平较低（p<0.001），（p=0.008），但血浆低密度脂蛋白胆固醇（LDL-C）（p=0.01）、总胆固醇（p=0.002），（p=0.03）和甘油三酯（TG）（p<0.001），（p=）水平分别高于APOE-ε3携带者。然而，APOE-ε2携带者仅血浆TG水平显著较高。在CAD/T2DM组和CAD/ND组患者中，APOE-ε4和ε2等位基因的比值比（OR）分别为2.98（p=0.001）、1.86（p=0.001）、2（p=0.001）和1.65（p=0.001）。

结论

本病例对照研究的主要发现是，在伊朗西部人群中，携带APOE-ε2和ε4等位基因的T2DM患者发生CAD的风险高于ND患者，与APOE-ε2等位基因相比，APOE-ε4与CAD的关联更为密切。这些结果表明，APOE-ε4等位基因携带者具有独特的血脂谱，该等位基因携带者HDL-C水平低、LDL-C水平高可能易患CAD和心肌梗死，尤其是糖尿病患者。这表明应考虑针对这些患者的治疗方式。