References:

Abbot MH, Murphy EA, Bolling DR, Abbey H (1974) The familial component in longevity, a study of the offspring of nonagenarians II. Preliminary analysis of the complete study. Johns Hopkins Med J.

Agundez JAG, Jimenez-Jimenez FJ, Luengo A, Bernal ML, Ayuso L, Vazquez A, Parra J, Duare J, Coria F, Ladero Alvarez JC, Benitez J () Association between polymorphism and early onset of Parkinson's disease. Clin Pharmacol Ther.

Agundez JAG, Menaya JG, Tejeda R, Lago F, Chavez M, Benitez () Genetic analysis of the NAT and CYP D polymorphisms in white patients with non-insulin-dependent diabetes mellitus. Pharmacogenetics.

Agundez JAG, Rodriguez I, Olivera M, Ladero JM, Garcia Ribera JM, Benitez J () CYP D , NAT and CYP E genetic polymorphisms in nonagenarians. Age Ageing.

Ayesh R, Idle JR, Ritchie JC, Crothers MJ, Hetzel MR () Metabolic oxidation phenotypes as markers for susceptibility to cancer. Nature.

Bell DA, Taylor JA, Butler MA, Stephens EA, Wiest J, LH, Kadlubae EF, Lucier GW () Genotype/phenotype concordance for human arylamine N-acetyltransferase (NAT) reveals a new slow acetylator allele common in Caucasians. Carcinogenesis.

Bordet R, Broly F, Deste A, Libersa C, Lafitte JJ () Lack of relationship between genetic polymorphism of cytochrome IID and sporadic idiopathic Parkinson's disease. Neuropharmacol.

Brockmuller J, Kerb R, Drakoulis N, Nitz M, Roots I () Genotype and phenotype of glutathione S-transferase class m zymes m and y in lung cancer patients and controls. Cancer.

Bulowvskaya LN, Krupin RG, Bochina TA, Shipova AA, MV () Acetylator phenotype in patients with breast oncology.

Cartwright RA, Glashan RW, Rogers HJ, Ahmad RA, D, Higgins E, Kahn MA () Role of N-acetyltransferase phenotypes in bladder carcinogenesis: pharmacogenetic logical approach to bladder cancer. Lancet.

All the genetically determined variations tested in this study were known to induce an impaired enzyme activity compared to the wild-type allele. Therefore, we were able to predict the corresponding phenotype of the individuals tested. We showed that none of the predicted phenotypes concerning debrisoquine hydroxylase-EM or -PM phenotypes, slow or fast N-acetylation capacities, and active or defective GST could be correlated with human longevity, either separately (Tables 24) or in combination for each individual (Table 5). Indeed, none of the possible combinations between these three predicted enzymatic activities was overrepresented in one population with respect to the other.

The influence of age on drug metabolism remains a matter for debate since some parameters of phenotyping are influenced by age while others are not (Siegmund et al. 1990; Laurent-Kenesi et al. 1996; Korrapati et al. 1997). Nevertheless, it is generally accepted that aging is associated with a reduction in functional liver mass and hepatic blood flow. Simple genotyping assays have been developed for a number of polymorphisms detected in xenobiotic-metabolizing enzyme genes, thus ruling out age or any other individual factor able to induce a misinterpretation of the final result. This kind of strategy proved to be effective.

References:

Cascorbi I, Drakoulis N, Brockmuller J, Maurer A, Sperling K, Roots I () Arylamine N-acetyltransferase (NAT) mutations and their allelic linkage in unrelated Caucasian individuals: correlation with phenotypic activity. Am J Hum Genet.

Cholerton S, Daly AK, Idle JR () The role of individual human cytochromes P in drug metabolism and clinical response. Trends Pharmacol Sci.

Daly AK, Thomas DJ, Cooper J, Pearson WR, Neal DE, Idle JR () Homozygous deletion of the gene for glutathione S-transferase M in bladder cancer. Br Med J.

Daly AK, Cholerton S, Armstrong M, Idle JR () Genotyping for polymorphism in xenobiotic metabolism as a predictor of disease susceptibility. Environ Health Perspect.

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