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 (I(2)) 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.