Polymorphisms of drug-metabolizing enzymes in healthy nonagenarians and centenarians: difference at GSTT1 locus

Biochem Biophys Res Commun. 2001 Feb 9;280(5):1389-92. doi: 10.1006/bbrc.2001.4280.

Abstract

Drug metabolizing enzymes are involved in the detoxification of several drugs, environmental substances, and carcinogenic compounds, and their polymorphisms have been associated with risk for a variety of cancer. In this paper, we compared the frequency of polymorphisms in cytochrome P450-1A1 gene (CYP1A1), a phase 1 gene (oxidation, activation), and of two polymorphisms of glutathione S-transferase enzymes (GSTM1, GSTT1), two phase 2 genes (conjugation, detoxification). Two groups were studied and compared, i.e., 94 nonagenarians and centenarians and 418 control subjects of younger age. A significant difference in the proportion of nonagenarians and centenarians homozygotes for a GSTT1 deletion (28%) was observed in comparison to control subjects (19%, P = 0.03). The distribution of the other gene polymorphisms did not differ in the two groups. These findings on phase 2 drug-metabolizing enzyme gene polymorphisms may help in disentangling gene-environmental interactions which can have a role in successful aging and longevity, as well as in cancer incidence in the oldest old.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Aging*
  • Child
  • Child, Preschool
  • Cytochrome P-450 CYP1A1 / genetics*
  • Cytochrome P-450 CYP1A1 / metabolism
  • Female
  • Gene Frequency
  • Genotype
  • Glutathione Transferase / genetics*
  • Glutathione Transferase / metabolism
  • Heterozygote
  • Homozygote
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Genetic*

Substances

  • Cytochrome P-450 CYP1A1
  • glutathione S-transferase T1
  • Glutathione Transferase
  • glutathione S-transferase M1