Polymorphic metabolic susceptibility genes and longevity: a study in octogonarians

• Published in: Toxicology letters Vol. 151; no. 1; pp. 283 - 290
• Main Authors: Pesch, Beate, Düsing, Rainer, Rabstein, Sylvia, Harth, Volker, Grentrup, Dagmar, Brüning, Thomas, Landt, Olfert, Vetter, Hans, Ko, Yon-Dschun
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 15.06.2004; Amsterdam Elsevier Science
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Ageing, cell death; Aging; Alleles; Aryl Hydrocarbon Hydroxylases - chemistry; Aryl Hydrocarbon Hydroxylases - genetics; Biological and medical sciences; Cell physiology; Cytochrome P-450; Cytochrome P-450 CYP1A1 - chemistry; Cytochrome P-450 CYP1A1 - genetics; Cytochrome P-450 CYP1B1; DNA - chemistry; DNA - genetics; Epidemiology; Female; Fundamental and applied biological sciences. Psychology; General aspects. Methods; Genetic Predisposition to Disease; Genetic Variation - genetics; Genetic Variation - physiology; Germany; Glutathione S-transferase; Glutathione Transferase - chemistry; Glutathione Transferase - genetics; Humans; Longevity; Longevity - genetics; Male; Medical sciences; Metabolism; Middle Aged; Molecular and cellular biology; Neoplasms - genetics; Polymerase Chain Reaction; Polymorphism, Genetic - genetics; Polymorphism, Genetic - physiology; Single nucleotide polymorphism; Toxicology; Tumors; Germany; OR; CI; Cytochrome P-450; Aging; GST; CYP; Single nucleotide polymorphism; Longevity; Metabolism; Glutathione S-transferase; Unspecific monooxygenase; Enzyme; Oldest old; Transferases; Cytochrome P450; Ageing; Genotype; Glutathione transferase; Molecular epidemiology; Drug-metabolizing enzyme; Oxidoreductases; Public health
• ISSN: 0378-4274; 1879-3169
• DOI: 10.1016/j.toxlet.2004.01.025

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.