Polymorphic metabolic susceptibility genes and longevity: a study in octogonarians.

Authors: Pesch B; Düsing R; Rabstein S; Harth V; Grentrup D; Brüning T; Landt O; Vetter H; Ko YD

Abstract: In order to investigate possible associations of genetic variants in genes of xenobiotic metabolism with longevity, we compared allele frequencies and genotype distributions of polymorphic genes between 205 octogenarians and a non-cancer reference group of 294 persons aged less than 80 years. We analyzed common sequence variations in the cytochrome P-450 genes CYP1A1 T461N, 3801 T > C and CYP1B1 V432L, and in the glutathione S-transferase genes GSTM1 (deletion), GSTT1 (deletion), and GSTP1 (I105V). In octogenarians, the CYP1B1 432L allele was less prevalent than in the reference group (allele frequency 0.49 versus 0.60; odds ratio, OR, 0.63, 95% confidence limits (CI) 0.40-1.00). Octogenarians turned out to have marginally significant more GSTM1 negatives (frequency 0.56 versus 0.48; OR 1.41, 95% CI 0.97-2.05), but less GSTT1 deficient genotypes (frequency 0.14 versus 0.21; OR 0.64; 95% CI 0.38-1.06). In octogenarians without cancer, GSTT1 negative carriers were less prevalent than in the aged with cancer (frequency 0.12 versus 0.27; OR 2.81; 95% CI 1.00-7.38). Polymorphic metabolic susceptibility genes could become relevant for processes of aging when toxic defense mechanisms decline.

Keywords: Adolescent; Adult; Aged; Aged, 80 and over; Alleles; Aryl Hydrocarbon Hydroxylases/chemistry/*genetics; Cytochrome P-450 CYP1A1/chemistry/*genetics; DNA/chemistry/genetics; Female; Genetic Predisposition to Disease; Genetic Variation/genetics/physiology; Germany; Glutathione Transferase/chemistry/*genetics; Humans; Longevity/*genetics; Male; Middle Aged; Neoplasms/genetics; Polymerase Chain Reaction; Polymorphism, Genetic/genetics/physiology
Journal: Toxicology letters
Volume: 151
Issue: 1
Pages: 283-90
Date: June 5, 2004
PMID: 15177664
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Citation:

Pesch B, Düsing R, Rabstein S, Harth V, Grentrup D, Brüning T, Landt O, Vetter H, Ko YD (2004) Polymorphic metabolic susceptibility genes and longevity: a study in octogonarians. Toxicology letters 151: 283-90.


Longevity Variant Associations (p-value):
  • rs1799814 (1.0)
  • rs4646903 (0.23)
  • rs1056836 (0.78)
  • rs1695

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