The ApoE gene is related with exceptional longevity: a systematic review and meta-analysis

The objective of this meta-analysis was to determine the association of the apolipoprotein E (ApoE) gene with exceptional longevity (EL) (i.e., reaching 100+ years) by identifying possible unequal distribution of alleles/genotypes in the common variants ε2, ε3, and ε4 among centenarians and younger population. The association of ApoE with EL was analyzed in a total of 2776 centenarians (cases) and 11,941 younger controls (from 13 case-control studies) using the chi-squared test with the Yates correction. We conducted combined and separate analyses for all ethnic groups studied in the literature (Caucasian and Asian). The main result for all ethnic groups combined was that the likelihood of reaching EL was negatively associated with ε4 allele carriage [pooled odds ratio (OR)=0.43; 95% confidence interval (CI) 0.36, 0.50; p<0.001] and with ε4/ε4 (OR=0.18; 95% CI 0.08, 0.39; p<0.001), ε3/ε4 (OR=0.44; 95% CI 0.37, 0.53; p<0.001) and ε2/ε4 genotypes (OR=0.48; 95% CI 0.31, 0.74; p<0.001). In contrast, the ε2/ε3 genotype was positively associated with EL (OR=1.35; 95% CI 1.06, 1.72; p=0.017). When compared with the ε3 allele, the ε2 allele was not associated with increased odds of EL (OR=1.08; 95% CI 0.77, 1.50, p=0.660). The present meta-analysis confirms that, besides its previously documented influence on Alzheimer's and cardiovascular disease risk, the ApoE gene is associated with the likelihood of reaching EL.