Type 2 diabetes mellitus (T2DM) is a highly complicated metabolic disorder for which there is worldwide effort for the identification of susceptibility genes. Polymorphisms of the Apolipoprotein E (ApoE) gene are associated with plasma lipid and lipoprotein levels and influence cardiovascular risk. Since insulin resistance is known to be strongly associated with metabolic dyslipidemia, ApoE polymorphisms have been implicated in predisposition to diabetes but the results of the individual studies were inconclusive. We present here a meta-analysis of population-based case-control genetic-association studies relating ApoE polymorphisms and T2DM. We included in the analysis 30 studies, which reported data of ApoE genotypes in 5423 T2DM patients and 8197 healthy unrelated controls. Multivariate and univariate methods suggest a significant role played by the E2 allele, since carriers of the E2 allele were at elevated risk for T2DM (Odds Ratio=1.18, 95% CI: 1.02, 1.35). There was no evidence for publication bias or other small-study related bias or significant heterogeneity in the analyses. Cumulative meta-analysis revealed no trend of the effect estimates over time and influential analysis excluded the possibility of a single influential study. E2 allele of ApoE seems to be a moderate risk factor for T2DM. Meta-regression analysis provided some weak evidence that the risk conferred by E2 allele is mediated through altering serum lipid levels (Total Cholesterol, LDL and HDL). Further studies are needed in order to elucidate the metabolic mechanism of this association as well as to study its effects on larger populations.

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