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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Apolipoprotein E2 / genetics*
  • Apolipoproteins E / genetics*
  • Case-Control Studies
  • Coronary Artery Disease / etiology*
  • Coronary Artery Disease / genetics*
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / genetics
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Middle Aged
  • Protein Isoforms / genetics
  • Risk Factors


  • Apolipoprotein E2
  • Apolipoproteins E
  • Protein Isoforms