Apolipoprotein E (ApoE) Gene Polymorphism and Cardiovascular Risk in Type 2 Diabetic Patients: A Systematic Review
Bibliographic record
Abstract
Background: Apolipoprotein E gene (ApoE) polymorphism has been extensively studied in the context of lipid metabolism and cardiovascular disease (CVD) risk. Its association with Type 2 Diabetes Mellitus (T2DM) patients presents a unique subset of cardiovascular risk due to underlying metabolic changes. This systematic review aims to summarize and critically evaluate the available evidence on the impact of ApoE gene polymorphism on cardiovascular risk among T2DM patients. Methods: We used the PEO (Population, Exposure and Outcome) framework to develop our protocol, which is publicly available in the Open Science Framework (OSF) registries. Following this protocol, a systematic search was conducted in PubMed, SCOPUS, and Google Scholar to identify studies focusing on adult individuals (≥ 18 years old) diagnosed with Type 2 Diabetes Mellitus (T2DM) that reported on ApoE gene polymorphisms. Only studies published in English between 2014 and 2024 were included. Three authors independently assessed the quality of the eligible studies using the Newcastle-Ottawa Scale (NOS) for case-control, cohort, and cross-sectional designs and the qualified studies were selected for full-text screening and data extraction. Results: 16 studies satisfied the quality assessment using the Newcastle-Ottawa Scale (NOS) with satisfying NOS scores included in the final review, which comprised 1 cohort study, 2 cross-sectional studies, and 13 case-control studies. Across the studies, E3/E3 is the dominant genotype in both control and T2DM populations. E3/E4 and E4/E4 genotypes are found to be significantly elevated in T2DM cases with cardiovascular risk factors compared to controls. The Ɛ3 allele is the most common across all populations, in most studies. The Ɛ4 allele is consistently strongly associated with elevated levels of low-density lipoprotein (LDL-C), total cholesterol, and triglycerides. Conclusion: Apolipoprotein E gene polymorphism is an evident risk factor for cardiovascular complications and ApoE genotyping will be a valuable tool for stratifying T2DM patients based on cardiovascular risk. HIGHLIGHTS Apolipoprotein E gene polymorphisms exert significant influences on lipid metabolism and cardiovascular risk among type 2 diabetes patients (T2DM). The Ɛ4 allele contributes to increased levels of low-density lipoprotein (LDL-C), total cholesterol, and triglycerides in T2DM patients. Apolipoprotein E gene genotyping can aid in stratifying cardiovascular risk in T2DM patients. The E3/E4 and E4/E4 genotypes are more frequent in T2DM patients with cardiovascular complications. GRAPHICAL ABSTRACT
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.007 | 0.028 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.008 | 0.006 |
| Bibliometrics | 0.008 | 0.010 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".