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
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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<0.001) among 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.
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Higher diastolic blood pressure has been observed in some cohorts.
“Diastolic blood pressure was elevated for male APOE4 carriers relative to non-carriers, consistent with a documented susceptibility of APOE4 carriers to cardiovascular risk factors [54], including higher diastolic blood pressure observed in some cohorts [55–57].”
From Effects of APOE2 and APOE4 on brain microstructure in older adults: modification by age, sex, and cognitive status (2024) · cites this paper as [57]
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“Diastolic blood pressure was elevated for male APOE4 carriers relative to non-carriers, consistent with a documented susceptibility of APOE4 carriers to cardiovascular risk factors [54], including higher diastolic blood pressure observed in some cohorts [55–57].”
Result
- Authors
- Sapkota, B., Subramanian, A., Priamvada, G., Finely, H., Blackett, P. R., Aston, C. E., & Sanghera, D. K.
- Affiliations
- University of Oklahoma Health Sciences Center (US)
- Corresponding author
- Sanghera, Dharambir K.
- Venue
- Journal of Diabetes and its Complications
- Publisher
- Elsevier BV
- Published
- 2015-11
- Volume
- 29
- Issue
- 8
- Pages
- 1191-1197
- ISSN
- 0891-6632 (ISSN-L)
- 1056-8727
- PMC
- PMC4656127
- OpenAlex
- W1105143468
- Cited by
- 25
- References
- 37
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 4 · 2023: 1 · 2022: 4 · 2021: 2 · 2020: 2 · 2018: 1 · 2017: 1 · 2016: 2
- FWCI
- 1.16
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Diabetes and its Complications (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Johns Hopkins University
- University of Oklahoma
- National Institutes of Health
- National Human Genome Research Institute
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK082766)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Keywords
- APOE polymorphism, apolipoprotein E, type 2 diabetes, coronary artery disease, cardiometabolic risk factors, APOE ε4, South Asian populations, metformin, sulfonylureas, diastolic blood pressure, HDL cholesterol, genetic susceptibility
- MeSH terms
- Alleles, Coronary Artery Disease, Diabetes Mellitus, Type 2, Diabetic Angiopathies, Drug Resistance, Drug Therapy, Combination, Female, Gene Frequency, Humans, Hyperglycemia, Hyperlipidemias, Hypoglycemic Agents, India, Male, Metformin, Middle Aged, Polymorphism, Genetic, Risk Factors, Sulfonylurea Compounds, Cohort Studies, Case-Control Studies, Genetic Predisposition to Disease, Apolipoprotein E3, Genetic Association Studies
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