Differences in the association between apolipoprotein E genotype and mortality across populations.

The gene for apolipoprotein-E (APOE) has three common alleles (epsilon2, epsilon3, and epsilon4) that have been shown to be associated with differences in the risk of death in persons older than 60 years in European populations. However, previous research suggests that they may not be associated with mortality in African Americans, and the evidence in Asians is mixed. It is now possible to examine the effects of these genotypes on mortality in African American, Chinese, Japanese, and Korean populations. The analysis is based on two types of published data: genotype by age and mortality by genotype. Demographic synthesis uses a multistate model to combine data from these case-control and cohort studies to provide maximum likelihood estimates of the relative risks of death. In general, the APOE epsilon2 allele is associated with 5%-10% lower mortality than the epsilon3/3 genotype. The epsilon4/4 allele is generally associated with a moderately high relative risk of death. The epsilon3/4 genotype is associated with 22% excess risk in Europeans and U.S. whites and with about 35% in Chinese. However, there is no evidence of excess risk with epsilon3/4 among African Americans and little excess risk among Japanese and Koreans. The relationship between genotype and mortality is consistent within these ethnic groups. For example, the estimates of R(3/4) for Japanese in Japan and Hawaii are both low, and the estimates for Chinese in Taiwan and Shanghai are relatively high. . The relationship between APOE genotype and mortality differs across population groups but shows little evidence of variation within groups.