Lack of association between human longevity and genetic polymorphisms in drug-metabolizing enzymes at the NAT2, GSTM1 and CYP2D6 loci |
| |
Authors: | M-L Muiras Patrick Verasdonck Florence Cottet François Schächter |
| |
Institution: | (1) Fondation Jean Dausset-CEPH, 27, rue Juliette Dodu, F-75010 Paris, France, FR;(2) DKFZ, Abteilung F0100, Im Neuenheimer Feld 242, D-69120 Heidelberg, Germany Tel.: +49-6221-42-4613; Fax: +49-6221-42-4962; e-mail: m.muiras@DKFZ-heidelberg.de, DE |
| |
Abstract: | In the present study, the possible role of genetic polymorphism of three drug-metabolizing enzymes, debrisoquine/sparteine
hydroxylase (CYP2D6), glutathione S-transferase μ (GSTM1), and N-acetyltransferase (NAT2), as a putative genetic component of human longevity, was explored. A total of 817 DNA samples from a centenarian and a control
(20–70 years) population was subjected to PCR-coupled RFLP methods. Subjects were genotyped for the CYP2D6*3 (A2637 deletion) and CYP2D6*4 (G1934A transition) alleles, for four mutations of NAT2 namely, NAT2*5A (C481T), NAT2*6A (G590A), NAT2*7A (G857A), and NAT2*14A (G191A)], and for the presence or absence of GSTM1 gene deletion. No significant difference was found at these three loci between centenarian and control subjects with respect
to allelic variant frequencies, genotype distributions or predicted phenotypes deduced from genotype combinations. By comparing
the distribution of combined genotypes for the polymorphisms tested at the CYP2D6, NAT2, and GSTM1 loci, none of the predicted phenotypes concerning debrisoquine hydroxylase extensive-metabolizer or poor-metabolizer phenotypes,
slow or fast N-acetylation capacities, and active or defective glutathione S-transferase, could be correlated with human longevity, alone or in combination.
Received: 4 September 1997/Accepted: 13 December 1997 |
| |
Keywords: | |
本文献已被 SpringerLink 等数据库收录! |
|