Aims: Due to the ever increasing incidence of T2DM, it is estimated that only half of the 79 million adults with type 2 diabetes (T2DM) will have adequate access to insulin by 2030 if the current levels of access is not improved. It is urgent to identify the important risk factors for T2DM and develop effective strategies to address the problem of T2DM. Our study aimed to evaluate the association between apolipoprotein E (ApoE) genetic polymorphism and type 2 diabetes, and to provide clues for the etiology of T2DM and even molecular marker of targeted therapy for the treatment of T2DM. Methods: Case-control studies of ApoE polymorphism and T2DM, which were included in PubMed, Web of Science, Medline, WanFang, VIP, and CNKI databases, were selected and evaluated according to criteria of inclusion and exclusion. Eligible data were extracted and pooled, and were analyzed and assessed using R soft-ware (version 3.4.3). Random-effect models were used when heterogeneity existed in between-study, and fixed-effect models were applied otherwise. Results: A total of 59 studies that consisted of 6,872 cases with T2DM and 8,250 controls were selected. Alleles and genotypes of ApoE between cases and controls were compared. For ApoE alleles, we observed the contrast ofϵ4 versus ϵ3 allele yielding a pooled OR of 1.18 (95% CI:1.09-1.28;P<0.001). For ApoE genotypes, compared with ϵ3/ϵ3 genotype,ϵ2/ϵ2 genotype showed a possible association with T2DM (OR=1.46; 95% CI:1.11-1.93, P=0.007), ϵ3/ϵ4 genotype had a 1.11-fold risk of developing T2DM (OR=1.11; 95% CI:1.01-1.22;P=0.039), and ϵ4/ϵ4 genotype had a 1.71-fold risk of developing T2DM (OR=1.71: 95% CI:1.33-2.19, P<0.001). Conclusions: There is an association between ApoE polymorphism and T2DM: allele ϵ4 and genotypes (ϵ2/ϵ2, ϵ3/ϵ4, and ϵ4/ϵ4) are associated with the increased risk for the development of T2DM, and they may be risk factors for T2DM.
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