Systemic lupus erythematosus (SLE) is a highly prevalent autoimmune disease and coronary artery disease (CAD) is a complication of SLE which is often crucial for the patient's prognosis. It is hypothesized that apolipoprotein E (Apo E), which is involved in cholesterol metabolism, might play a role in this process.Patients with SLE registered at the University of Toronto Lupus Clinic who had DNA available for study had their Apo E genotype determined. Each case was assessed for the presence of CAD, and Apo E allele frequencies in patients with SLE were compared with data from the general population. Age at onset and disease duration of CAD were also recorded and compared between groups.DNA was stored from 152 patients, of whom 38 (25%) had CAD. There was no difference in the frequencies of the Apo E isoforms between SLE patients and the general population. Patients with the E2 allele developed CAD after a mean +/-SD of 6.0+/-1.9 yrs compared with 14.5+/-5.4 yrs in those with E3/3 (p<0.01).The distribution of Apo E genotypes in SLE is not significantly different from that of the North American population. In SLE, Apo E2 was associated with a more rapid development of CAD. Therefore, Apo E2 might interact with other disease-related factors to accelerate the onset of CAD in some patients with SLE and as such might be an additional marker of risk in this population.