Apolipoprotein E Genotype and Gallbladder Disease Risk in a Large Population-Based Cohort

Purpose: The aim of the study is to describe the association between apolipoprotein E (apoE) genotype and gallbladder disease incidence. Methods: Cases of incident hospitalized gallbladder disease were ascertained in nearly 13,000 middle-aged men and women participating in the Atherosclerosis Risk in Communities (ARIC) Study, a prospective cohort study in four US communities. Results: Between the ARIC baseline examination (1987 to 1989) and December 31, 2001, a total of 639 participants were hospitalized for gallbladder disease. After adjustment for age, sex, race, obesity, plasma lipid level, and diabetes, the relative risk for hospitalized gallbladder disease associated with the presence of an ε4 allele (i.e., genotypes E4/4, E3/4, and E2/4 versus other genotypes) was 0.72 (95% confidence interval [CI], 0.60-0.87). Stratification by race showed that the inverse association with ε4 was stronger in whites (relative risk, 0.69; 95% CI, 0.56-0.85) than African Americans (relative risk, 0.86; 95% CI, 0.58-1.30). The presence of the other rare isoform, ε2 (i.e., genotypes E2/2, E2/3, and E2/4 versus others) was associated with a modest increased risk for gallbladder disease (relative risk, 1.28; 95% CI, 1.05-1.57). Conclusions: These results suggest that independent of traditional risk factors, apoE genotype may influence gallbladder disease risk, particularly in whites. The exact biologic mechanism for such an association remains unclear and requires further investigation.