Association of APOE polymorphisms with diabetes and cardiometabolic risk factors and the role of APOE genotypes in response to anti-diabetic therapy: results from the AIDHS/SDS on a South Asian population

Background and Objectives Apolipoprotein E ( APOE ) gene polymorphisms have been examined extensively in multiple global populations particularly due to their crucial role in lipid metabolism and cardiovascular disease. However, the overall contribution of APOE polymorphisms in type 2 diabetes (T2D) and coronary artery disease (CAD) in South Asians is still under-investigated. The objectives of this investigation were: 1) to evaluate the distribution of APOE polymorphisms in a large diabetic case–control sample from South Asia, 2) to examine the impact of APOE polymorphisms on quantitative risk factors of T2D and CAD, and 3) to explore the contribution of APOE genotypes in the response to anti-diabetic therapy. Subjects and Methods A total of 3564 individuals (1956 T2D cases and 1608 controls) used in this study were part of the Asian Indian Diabetic Heart Study/Sikh Diabetes Study (AIDHS/SDS). We assessed the association of APOE polymorphisms with T2D, CAD and cardiometabolic traits using logistic and linear regression analysis. Results and Conclusions No significant differences in the distribution of APOE genotypes were observed between T2D and CAD cases and controls. The APOE4 genotype carriers had moderately higher diastolic blood pressure (BP) (p=0.022), and lower HDL-cholesterol (p=0.026) compared to E4 non-carriers. Overall, the APOE genotype was not a significant predictor of cardiometabolic disease in this population. Further stratification of data from diabetic patients by APOE genotypes and anti-hyperglycemic agents revealed a significant (~23%) decrease in 2-hour glucose (p=0.004) and ~7% decrease in systolic BP (p APOE4 carriers compared to non-carriers on metformin and sulphonylurea (SU) combination therapy, and no such differences were seen in patients on other agents. Our preliminary findings point to the need for evaluating population-specific genetic variation and its interactions with therapeutic effects.