The apolipoprotein epsilon2 allele and the severity of coronary artery disease in Type 2 diabetic patients.

AIMS: To examine the hypothesis that apolipoprotein E2 is associated with more severe coronary disease in Type 2 diabetic patients.

RESEARCH DESIGN AND METHODS: In this retrospective cohort study, 491 patients with angiographically assessed coronary disease were recruited from those attending a university hospital cardiology department. Participants completed detailed questionnaires, from which the presence or absence of diabetes was determined. Fasting blood samples were obtained for apolipoprotein E genotype and measurement of blood lipid parameters.

RESULTS: The prevalence of triple vessel disease was significantly lower in non-diabetic, epsilon2 allele carriers (39.3% vs. 16.2%; odds ratio (OR) 0.30 (0.12-0.71), P < 0.03) compared with E3/3 carriers. In Type 2 diabetic patients, epsilon2 allele carriers had an excess of triple vessel disease compared with E3/3 genotypes (43.3 vs. 68.8%; OR 2.8 (1.07-7.30), P < 0.05). The differences were independent of other variables. The apo E4 subgroup showed no significant differences in the frequency of triple vessel disease.

CONCLUSIONS: Diabetic epsilon2 allele carriers had more severe coronary artery disease than diabetic patients with other apo E isoforms. In non-diabetic patients the epsilon2 allele appeared to protect against severe coronary disease. We hypothesize that interaction between the diabetic milieu and the epsilon2 allele accelerates plaque progression. It suggests that diabetic patients who are carriers of the epsilon2 allele, even in the heterozygous form, should be the focus of particular therapeutic attention. Diabet. Med. 18, 445-450 (2001)