Gallstone cholesterol content is related to apolipoprotein E polymorphism

Background: The genetically determined phenotypes of apolipoprotein E are related to variations in lipoprotein levels and in the enterohepatic metabolism of cholesterol and bile acids. The present study was designed to elucidate the role of apolipoprotein E polymorphism in gallstone formation. Methods: Apolipoprotein E phenotype was determined in 169 consecutive cholecystectomy patients and in 200 controls. The cholesterol content of the gallstones (n = 169), the presence of cholesterol monohydrate crystals of fresh gallbladder bile (n = 142), and the nucleation time (n = 35) were also analyzed. Results: The median cholesterol content of the gallstones was higher in the apolipoprotein E4 category (phenotypes E4/4 and E4/3, 97%) than in the E3 (E3/3, 78%) and E2 patients (E2/2 and E2/3, 76%, P = 0.0003). In E4 patients, cholesterol crystals were found immediately after surgery in 27 of 40 (68%), whereas in E3 and E2 groups in 36 of 88 (41%), and 4 of 14 (29%) of the patients (P = 0.0001). The median nucleation time in E4 patients (2.5 days) was shorter than in patients with E3 (5.5 days) or E2 (6.0 days) (P = 0.0016). Conclusions: These data indicate that apolipoprotein E polymorphism affects cholesterol content of cholelithiasis. We suggest that this phenomenon is mediated by the altered formation of cholesterol monohydrate crystals in different apolipoprotein E phenotypes.