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Several previous association studies carried out in Cau- casian and Asian populations have shown contradictory re- sults in relation to the role of APOE and ACE polymorphisms in human longevity. In addition to varia- tions in genetic risks between populations, differences in the composition of younger and older subject samples (for example, presence of comorbidity) between studies may partially explain the variability in their results (2,7).

phisms in human longevity in Caucasian and Asian popula- tions. A systematic review showed that the association of APOE with longevity is dependent on the frequency of APOE4 in young subjects, being lower or nonsignificant in samples with a low APOE4 frequency (21,22). These observations and the low frequency of APOE4 in our young population (9%) may explain our current findings of lack of association with APOE4.

Although previous reports in Europe and Asia showed that there were no differences in ACE genotypes with age or a paradoxical decrease in ACE II genotype (23–33), a re- cent report showed a decrease of ACE DD genotype (34) (O60 vs. O70 years, 45 vs. 42%) in a smaller sample of older subjects of mixed descent living in Brazil. The age-dependent decrease and negative selection of ACE DD genotype carriers is compatible with its associated risk for cardiovascular diseases in Caucasian populations (10). Results of prospective studies analyzing mortality in small time windows (2–10 years) are also inconclusive in relation to effects of ACE and APOE polymorphisms (35,36).

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