The ApoE gene is related with exceptional longevity: a systematic review and meta-analysis.
Level 3 - non-randomized controlled study
Systematic review and meta-analysis of observational case-control studies
PubMed 25385258 · doi:10.1089/rej.2014.1605
What was done
Authors conducted a systematic review and meta-analysis of 13 case-control studies comprising 2,776 centenarians (cases, age 100+ years) and 11,941 younger controls. They evaluated the distribution of apolipoprotein E (ApoE) common variants (ε2, ε3, and ε4 alleles and genotypes) in combined and separate analyses of Caucasian and Asian populations using chi-squared tests with Yates correction.
What was found
Across all ethnic groups combined, reaching exceptional longevity was negatively associated with ε4 allele carriage (pooled OR = 0.43; 95% CI 0.36 to 0.50; p < 0.001) and with specific ε4-bearing genotypes: ε4/ε4 (OR = 0.18; 95% CI 0.08 to 0.39; p < 0.001), ε3/ε4 (OR = 0.44; 95% CI 0.37 to 0.53; p < 0.001), and ε2/ε4 (OR = 0.48; 95% CI 0.31 to 0.74; p < 0.001). Conversely, the ε2/ε3 genotype was positively associated with longevity (OR = 1.35; 95% CI 1.06 to 1.72; p = 0.017). The ε2 allele alone, compared directly with the ε3 allele, was not significantly associated with exceptional longevity (OR = 1.08; 95% CI 0.77 to 1.50; p = 0.660).
Why it matters
This study provides robust pooled quantification showing that ApoE ε4 is strongly depleted among centenarians, establishing that ApoE variation relates to overall exceptional survival beyond its established links to Alzheimer's and cardiovascular disease.
Limits
All included studies were retrospective case-control comparisons rather than longitudinal prospective cohorts, which creates birth-cohort and survival selection effects. Data were limited to Caucasian and Asian populations, precluding generalization to other ethnic groups. The abstract does not report adjustments for lifestyle factors or environmental covariates.
Cited by
- supports ApoE4 is significantly underrepresented among centenarians.