6. Caporaso N, Land! MT, Vineis P. Relevance of polymorphisms to human carcinogenesis: evaluation of epidemiologic evidence. Pharmacogenetics 1991; 1: 4-19.

Our findings, showing identical prevalence of mutations and, more importantly, identical prevalence of functional genes in nonagenarians and in younger controls, indicate that, in the drugs metabolized by such enzymes, pharmacokinetic differences due to decreased metabolism should be attributed to decreased liver blood flow rather than a genetic selection in very old people. Pharmacodynamic differences between elderly people and younger subjects, due to differences in tissue drug metabolism, should not be expected with drugs that are metabolized by these enzymes.

7. Hayashi SI, Watanabe J, Kawajiri K. Genetic isms in 5'-flanking region change transcriptional regulation of the human cytochrome P45OIIE1 gene. J Biochem 1991; 559-65.

8. Guengerich FP, Kin D-H, Iwasaki M. Role of cytochrome P-450 IIE1 in the oxidation of many molecular weight cancer suspects. Chem Res Toxicol 1991; 4: 168-79.

9. Ladero JM, Agundez JAG, Rodriguez-Lescure A, Rubio M, Benftez J. Rsal polymorphism at the P4502E1 and risk of hepatoceUular carcinoma. Gut 1996;

10. Agundez JAG, Jimenez-Jimenez FJ, Luengo A, et al. ation between the oxidative polymorphism and early onset of Parkinson's disease. Clin Pharmacol Ther 1995; 57: 291-8.

• There are no specific combinations of CYP

E

and NAT

genotypes associated with extreme longevity. The distribution of these types is similar in healthy very old people to that the general population. • Other factors, not only genetic but also related life style, determine the chance of reaching advanced age. • It is reasonable to use younger control when studying the distribution of these polymorphisms in diseases affecting older groups.

from http://ageing.oxfordjournals.org/ by guest on March 23, 2016

11. Neitzel HA. A routine method for the establishment of permanent growing lymphoblastoid cell lines. Hum Genet 1986; 73: 320-2.

12. Martinez C, Agundez JAG, Olivera M, Martin M, JM, Benitez J. Lung cancer and mutations at the NAT2 gene locus. Pharmacogenetics 1995; 5: 207-14.

13. Agundez JAG, Ledesma MC, Ladero JM, Benitez Prevalence of CYP2D6 gene duplication and its on the oxidative phenotype in a white population. Clin

14. Stephens EA, Taylor JA, Kaplan N, et al. Ethnic in the CYP2E1 gene: polymorphism analysis of 695 Americans, European-Americans and Taiwanese. Pharmaco-

Acknowledgements

We thank Mr Luis Lozano for excellent technical assistance. Supported in part by Grants CICYT- SAF92-0333 from Comision Interministerial de Cien- cia y Tecnologia (Madrid) and FISss 93/0632 and 94/0326 from Fondo de Investigaciones sanitarias de la Seguridad Social (Madrid). This study was carried out in coordination with COST Biphase m.

15- Agundez JAG, Martinez C, Ladero JM, etal. oxidation genotype and susceptibility to lung cancer. Pharmacol Ther 1994; 55: 10-4.

16. Ladona MG, Abildua RE, Ladero JM, et al. genotypes in Spanish women with breast cancer. Cancer Lett 1996; 99: 23-8.

17. Agundez JAG, Ledesma MC, Benitez J, et al. genes and liver cancer risk. Lancet 1995; 345: 830-1.

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