APOE gene polymorphisms and susceptibility to Creutzfeldt–Jakob disease

Associations between apolipoprotein E (APOE) gene polymorphisms and Creutzfeldt–Jakob disease (CJD) have been reported, but the results from many of these studies are conflicting. To investigate the association between APOE polymorphisms and CJD risk, we performed a meta-analysis. We used odds ratios (OR) with 95% confidence intervals (CI) to assess the strength of the association. The frequency of putative risk alleles in control subjects was estimated with the Mantel-Haenszel method. Cochran’s Q statistic and the inconsistency index (I2) were used to test heterogeneity. Egger’s test and an inverted funnel plot were used to assess bias. Our study included 11 published case–control studies with APOE genotyping, involving a total of 1001 CJD patients and 1211 controls. Overall, the APOE 34 (OR 1.37, 95% CI: 1.09–1.72), and APOE 44 (OR 3.16, 95% CI: 1.37–7.26) genotypes and the APOE 4 (OR 1.41, 95% CI: 1.08–1.85) allele were associated with an increased risk of CJD, and the APOE 33 (OR 0.81, 95% CI: 0.67–0.97) genotype tended to protect against CJD. However, we did not find significant evidence supporting associations of the APOE 22 (OR 1.15, 95% CI: 0.45–2.93), APOE 23 (OR 0.84, 95% CI: 0.64–1.09), or APOE 24 (OR 1.40, 95% CI: 0.70–2.77) genotypes, nor the APOE 2 (OR 1.02, 95% CI: 0.73–1.42) or APOE 3 (OR 0.82, 95% CI: 0.65–1.02) alleles with CJD using a fixed-effects model. Our results support a genetic association between APOE polymorphisms and CJD.