Except for the rare epsilon 22 genotype it remains largely unsettled whether apolipoprotein E genotype influences an individual's referral to lipid clinics. To test this hypothesis, we compared genotype distributions among 156 hypercholesterolemic and 83 hypertriglyceridemic patients attending a lipid clinic with that among 9241 individuals sampled from the Danish general population. The relative genotype frequencies of epsilon 22, epsilon 32, epsilon 42, epsilon 33, epsilon 43, and epsilon 44 were 0.005, 0.126, 0.026, 0.564, 0.251, and 0.027 in the general population, which differed from genotype frequencies in both hypercholesterolemic (chi (2): P = 0.01) and hypertriglyceridemic patients (chi (2): p < 0.001). BY comparison with <epsilon>33, epsilon 44 predicted a 2-fold increase whereas epsilon 32 predicted a 2-fold decrease in the attendance rate at the lipid clinic for hypercholesterolemic patients (95% confidence intervals: 1.1-4.3 and 0.2-0.9). Among hypertriglyceridemic patients, epsilon 22, epsilon 42, epsilon 43, and epsilon 44 versus epsilon 33 predicted 13-, 3-, 11/2-, and 3-fold attendance rates at the lipid clinic, respectively (95% confidence intervals: 4.5-39.9, 1.2-8.4, 1.0-2.8, and 1.1-7.6). These findings are in accordance with the fact that epsilon 44 raises cholesterol levels, epsilon 32 reduces cholesterol levels, and epsilon 22, epsilon 42, epsilon 43, and epsilon 44 raise triglyceride levels in comparison with epsilon 33. These data suggest that hypercholesterolemic individuals carrying epsilon 44 and hypertriglyceridemic individuals carrying epsilon 22, epsilon 42, epsilon 43, or epsilon 44 are relatively more often referred to lipid clinics than carriers of epsilon 33. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.