be paradoxical, due to the previously reported associations of ACE1*D allele with elevated circulating plasma ACE1 levels and increased risk of myocardial infarction and CAD (Cambien et al., 1992). However, there might, as yet, be some unknown benefit from the inheritance of the ACE1*D allele. For example, the involvement of ACE1 polymorph- ism in a wide range of cellular functions, such as repair to damaged tissues as well as or in addition to reported resistance to neoplasia or infection all of which would favour increased survival rates (Costerousse et al., 1992; Eisenlohr et al., 1992). Furthermore, the unexpected association of ACE1*D/D with longevity (Schachter et al., 1994) might be somehow linked to the recent, suggested relationship between reduced risk of AD development on inheritance of the ACE1*D allele with AD (Kehoe et al., 1999). Two separate studies have attempted but have failed to replicate the original longevity findings (Bladbjerg et al., 1999; Blanche` et al., 2001). An additional case-referent and retrospective cohort study in a Danish population revealed that the relative frequencies of ACE1*D/*D genotype and ACE1*D allele were statistically unaffected by age in both women and men, suggesting that the ACE1 gene polymorphism did not influence longevity (Agerholm-Lar- sen et al., 1997). In a previous study of British subjects aged 84 and older the authors reported a significant difference in ACE1 genotype frequencies in elderly men

edge that the comparison of our allele and genotype frequencies with other published studies has to be considered with some caution since published data will have been generated in different laboratories, with slightly differing methodologies, and thus there is a possibility of discrepancies in genotype classification (Ueda et al.,1996). However, in defence of this, the data presented by Blanche` and colleagues actually involved the re-genotyping of ACE1, in the original 1994 centenarian cohort of Shachter, with a more reliable two-step method (Rigat et al., 1992; Lindpaintner et al., 1995), as used by us and they described only a 5% deviation from the original genotypes that were homogenously distributed across all genotypes (Blanche` et al., 2001). Furthermore, the study on Danish centenarians (Bladbjerg et al., 1999) also utilized a similar method of ACE1 genotyping that included a third internal PCR primer (Evans et al., 1994). Indeed, even with the

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