No association between APOE ε 4 allele and multiple sclerosis susceptibility: a meta-analysis from 5472 cases and 4727 controls

Background: Apolipoprotein E (APOE) gene ε4, 2 alleles have been reported to be associated with multiple sclerosis (MS), but results were conflicting. In order to derive a more precise estimation of the associations, a meta-analysis was performed.

Methods: The PubMed, EBSCO and BIOSIS databases were searched to identify eligible studies published in English before March, 2011. Data were extracted using standardized forms. The association was assessed by odds ratio (OR) with 95% confidence intervals (CIs). Begg's test was used to measure publication bias.

Results: A total of 20 case-control studies, containing 5472 patients/4727 controls for ε4 allele and 4636 patients/4047 controls for ε2 allele were included. The associations between APOE ε4, 2 alleles and MS were not found in overall population (OR(ε4)=0.997, 95% CI=0.861-1.156; OR(ε2)=1.097, 95% CI=0.940-1.279). Subgroup analysis revealed that APOE ε4, 2 alleles were not associated with an increased risk of MS in Caucasian population (OR(c-ε4)=0.924, 95% CI=0.819-1.041; OR(c-ε2)=1.127, 95% CI=0.955-1.331). There was no evidence of publication bias according to Begg's regression test.

Conclusions: This meta-analysis suggests that APOE ε4, 2 alleles are not associated with MS susceptibility. However, large sample, representative population-based studies with homogeneous MS patients, and well matched controls are warranted to confirm this finding.