Non-invasive methodologies allowed us to detect CYP2D6*3 and CYP2D6*4 alleles, the wild-type allele and four main mutations of the NAT2 gene, and null- and wild-type alleles of GSTM1 in DNA samples from cente- narian and control populations. This study did not aim to extensively study all the reported mutations of CYP2D6, NAT2, and GSTM1 since a number of inactivating muta- tions have now been identified which were not detectable with the methods used here. It is thus important to note that the DNA-based genetic assay we used identifies up to 90% of CYP2D6 PM individuals (Smith et al. 1992) and allows positive identification of greater than 90% of all slow acetylators (Hickman and Sim 1991; Bell et al. 1993).

Acknowledgements We want to thank M. Legrand, C. Billon, L. Cazes, and F. Dufour, for technical assistance; I. Lafourcade and N. Gauthier, as well as many physicians, for their help in collecting the centenarian blood samples. We are very grateful to Dr. A. Bürkle, Dr. P.U. Giacomoni, and Dr. G. Thomas for helpful discussions and advice on the manuscript reduction, and Dr. S. Panserat for useful technical advice. This work was supported by the Concerted Action Programme on Molecular gerontology: the identification of links be- tween ageing and the onset of age-related diseases (MOLGERON), sponsored by the EU Commission (BMH1 CT94 1710) (F.S.) and in part by L’Oréal, Laboratoire de Recherche Avancée, Clichy (France) (M.L.M.).

By comparing allele or genotype distributions in the two populations for the three loci, no statistically signifi- cant difference was found between the two populations. Normal individuals had been recruited for the CEPH cell bank not based on any disease characteristics but based on a large sibship size as an informative element for linkage mapping. Thus, some bias due to the genetic characteris- tics of the control population with respect to slow- acetylator allele frequency cannot definitely be ruled out since, in our sampled populations, it was higher than in many studies of USA and European Caucasian populations (Bell et al. 1993). Nevertheless, numerous investigators have reported not only ethnic but also geographical varia- tion in the slow-acetylation phenotype, the percentage of which spans from about 10% in the Japanese population to more than 90% in some Mediterranean peoples (Hirvonen 1995).

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