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Association of apolipoprotein E polymorphisms (E2, E3, E4) with type 2 diabetes: a meta-analysis of case-control
Chaimae Zouine1,2, Mohamed Amine Ikhanjal1,3, Khaoula Errafii4
1Virology Environmental Health Laboratory, Institut Pasteur du Maroc, Casablanca, Morocco.
The Pan African Medical Journal
|June 12, 2026
Summary
The apolipoprotein E (APOE) E4E4 genotype and E4 allele are significantly associated with an increased risk of type 2 diabetes (T2D). This finding clarifies genetic links to T2D across diverse populations.
Area of Science:
- Genetics and Epidemiology
- Metabolic Diseases Research
Background:
- Type 2 diabetes (T2D) is a complex disease influenced by genetic and environmental factors, with apolipoprotein E (APOE) gene polymorphisms showing varied associations with T2D risk across populations.
- Understanding the specific role of APOE genotypes and alleles in T2D susceptibility is crucial for targeted prevention and treatment strategies.
Purpose of the Study:
- To conduct a meta-analysis clarifying the association between APOE genotypes (E2E2, E2E3, E2E4, E3E4, E4E4) and alleles with type 2 diabetes (T2D) risk.
- To examine demographic, clinical, and biochemical parameters associated with T2D risk in cases versus controls.
Main Methods:
- Systematic literature search of PubMed, Google Scholar, Web of Science, and Science Direct for human case-control studies on APOE polymorphisms and T2D.
- Meta-analysis of data from 32 studies involving 19,644 participants, using Review Manager 4.3.1.
- Assessment of publication bias and heterogeneity using Q test and Egger regression analysis.
Main Results:
- The APOE E4E4 genotype (OR=1.94) and E4 allele (OR=1.26) were significantly associated with an increased risk of T2D.
- No significant associations were found for APOE genotypes E2E2, E2E3, E2E4, E3E4, or the E2 allele.
- Body Mass Index (BMI), Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Total Cholesterol (TC), and LDL-C were potential indicators of higher T2D risk.
Conclusions:
- This meta-analysis confirms a significant association between the APOE E4E4 genotype and E4 allele with an elevated risk of type 2 diabetes.
- The findings contribute to understanding the genetic predisposition to T2D, particularly the role of APOE variants.
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