The presence of apolipoprotein ε4 and ε2 alleles augments the risk of coronary artery disease in type 2 diabetic patients

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-ε4 and ε2 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-ε4 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-ε3 carriers, respectively. However, carriers of APOE-ε2 had significantly higher levels of plasma TG only. OR of APOE-ε4 and ε2 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-ε2 and ε4 alleles have a higher risk of developing CAD than ND patients in the western population of Iran, with APOE-ε4 being more closely associated with CAD than the APOE-ε2 allele. These results indicated that carriers of APOE-ε4 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.