The role of apolipoprotein E and glucose intolerance in gallstone disease in middle aged subjects

Background-The polymorphism of apolipoprotein E has been suggested to be associated with the cholesterol content of gallstones, the crystallisation rate of gall bladder bile, and the prevalence of gallstone disease (GSD). Aims-To investigate whether apolipoprotein E polymorphism modulates the susceptibility to GSD at the population level and to study the possible associations between impaired glucose tolerance, diabetes, and GSD. Methods-Apolipoprotein E phenotypes were determined in a middle aged cohort of 261 randomly selected hypertensive men, 259 control men, 257 hypertensive women, and 267 control women. All subjects without a documented history of diabetes were submitted to a two hour oral glucose tolerance test (OGTT), GSD was verified by ultrasonography. Results-In women with apolipoprotein E2 (phenotypes E2/2, 2/3, and 2/4) compared with women without E2 (E3/3, 4/3, and 4/4), the odds ratio for GSD was 0.28 (95% confidence interval 0.08-0.92), There was no protective effect in men. The relative risk for GSD was 1.2 (0.8-1.7) for hypertensive women and 1.8 (1.0-2.7) for hypertensive men. In a stepwise multiple logistic regression model, E2 protected against GSD in women, whereas two hour blood glucose in the OGTT, serum insulin, and plasma triglycerides were risk factors. Elevated blood glucose during the OGTT was also a significant risk factor for GSD in men. Conclusions-The data suggest that apolipoprotein E2 is a genetic factor providing protection against GSD in women. In contrast, impaired glucose tolerance and frank diabetes are associated with the risk of GSD.