Apolipoprotein E genotype and mortality in Southern European and Anglo-Celt patients with type 2 diabetes: The Fremantle Diabetes Study

Abstract

Objective: To determine whether cardiac and all-cause mortality are lower in Southern European (SE) patients than in Anglo-Celt (AC) patients with type 2 diabetes in an urban Australian setting, and, if so, whether ethnicity-specific differences in apolipoprotein E (APOE) genotypes are contributory. Design: Longitudinal observational cohort study. Methods: We analysed detailed data from 1057 patients from the community-based Fremantle Diabetes Study, 238 were of an SE migrant background and 819 of AC ethnicity. Cox proportional hazards modelling was used to identify independent predictors of cardiac and all-cause mortality. Results: During 9.8±3.5 years of follow-up, 411 (38.9%) participants died, 161 (39.2%) from cardiac causes. Significant positive baseline independent predictors of cardiac death were age, male gender, coronary heart disease, cerebrovascular disease, peripheral arterial disease, retinopathy and peripheral neuropathy (P≤0.004), while maternal history of diabetes was protective (P=0.014). After adjusting for these variables, APOE4 carriage was predictive (hazard ratio (95% confidence interval) 1.61 (1.01-2.58); P=0.048). SE ethnicity did not add significantly to the model either as a single variable or as an interaction term with APOE4 carriage (P≥0.86). Significant independent predictors of all-cause mortality were age, male gender, smoking, coronary heart disease, cerebrovascular disease, peripheral arterial disease, retinopathy, peripheral neuropathy and microalbuminuria (P≤0.047), while overweight/obesity, lipid-lowering therapy and recent exercise were protective (P≤0.008). APOE4 carriage, SE ethnicity and their interaction did not add to the model (P≥0.32). Conclusions: SE ethnicity does not confer an independent survival advantage in community-based Australian type 2 diabetic patients, but APOE4 carriers are at higher risk of cardiac death. © 2010 European Society of Endocrinology.