Association study between DNA methylation and genetic variation of APOE gene with the risk of coronary artery disease

Document Type : Original article

Authors

1 Department of Pharmacology, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran

2 Department of Hematology and Blood Transfusion, School of Allied Medical Sciences, Lorestan University of Medical Sciences, Khorramabad, Iran

3 Department of Medical Laboratory Sciences, School of Paramedical Sciences, Zanjan University of Medical Sciences, Zanjan, Iran

Abstract

Coronary artery disease (CAD) is a common health problem with a high rate of disability and death. Dyslipidemia and altered metabolism of Apo-lipoproteins are involved in the CAD pathogenesis. The current study investigated two common polymorphisms (rs429358 and rs7412) and promoter DNA methylation status of APOE in the Iranian CAD patients and control subjects. Two hundred angiographically documented CAD patients and 200 control subjects were included in the study. The APOE polymorphism analysis was done by PCR-RFLP technique and DNA methylation status was evaluated by methylation specific PCR. The assay of lipid levels was conducted using standard colorimetric protocols.Results indicated that the frequency of ε3/ε4 and ε2/ε3 genotypes was significantly more common in CAD group compared with control group. Relative to wild type genotype (ε3/ε3), CAD patients with ε3/ε4 and ε2/ε3 genotypes displayed significantly higher concentration of total-cholesterol and LDL-cholesterol. The frequency of DNA methylation of APOE was similar between the two studied groups. However, the methylation frequency of APOE gene was significantly higher in triple stenotic vessels relative to single stenotic vessels (P=0.032). In conclusion The present study indicated that the rs429358 and rs7412 polymorphisms are significantly risk factors for development and severity of CAD. Also, APOE methylation status may be involved in the severity but not in the development of CAD.

Keywords


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