Abstract Body: Background: Apolipoprotein E is an essential component of lipoprotein metabolism and it is modulated by the ApoE gene. This gene has three known polymorphic variants: ε2, ε3 and ε4. Several studies showed that the presence of these polymorphisms may increase the risk of cardiovascular diseases (CVD) like coronary artery disease (CAD), peripheral artery disease (PAD), heart failure (HF), atherosclerosis and stroke, especially in type 2 diabetes mellitus (T2DM) patients.
Objective: This systematic review aims to evaluate the impact of ApoE gene polymorphisms on the risk of developing cardiovascular disease (CVD) in T2DM patients.
Methods: We performed a comprehensive search in the following databases: PubMed, ScienceDirect, and Google Scholar. All observational studies available in English, that provided full text and published before July 2024 were included. Studies were chosen based on the documentation of ApoE gene polymorphisms and their correlation with cardiovascular diseases in individuals with Type 2 diabetes mellitus (T2DM). A qualitative synthesis of the findings was conducted to summarize the associations observed across the studies. Due to heterogeneity of the population characteristics and outcome measures in the included studies, we were not able to conduct statistical testing.
Results: A total of 17 studies involving 9,497 participants were included in this review. Results from 11 studies (6 focusing on CAD, 2 on PAD, 1 on CAD+cerebral infarction, 1 on HF and 1 on diabetic atherosclerosis) concluded that there was an increased frequency of the ε3/4 genotype among T2DM patients with CVD and that the presence of the ε4 allele significantly increased the risk of CVD. Ten studies showed that individuals with ε4-bearing genotypes, particularly ε3/4, had lower levels of plasma high-density lipoprotein cholesterol (HDL-C) and higher levels of plasma low-density lipoprotein cholesterol (LDL-C) and total cholesterol. There were two studies on stroke in T2DM patients which reported that the ε2/ε3 genotype was associated with an increased risk of ischemic stroke. Two studies also showed that the presence of ε2 allele may provide certain protection against CVD.
Conclusion: ApoE gene polymorphisms, particularly the ε4 allele, are associated with an increased risk of CVD and altered plasma lipid profiles in T2DM patients. These findings suggest that ApoE gene polymorphisms can be a potential screening tool to assess CVD risk in diabetic patients.