title: Polymorphic metabolic susceptibility genes and longevity: a study in octogonarians.
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.
authors.affiliation: Berufsgenossenschaftliches Forschungsinstitut für Arbeitsmedizin, Ruhr-Universität Bochum, Bürkle-de-la-Camp-Platz 1, Bochum D-44789, Germany.
authors.forename: Beate
authors.initials: B
authors.lastname: Pesch
authors.forename: Rainer
authors.initials: R
authors.lastname: Düsing
authors.forename: Sylvia
authors.initials: S
authors.lastname: Rabstein
authors.forename: Volker
authors.initials: V
authors.lastname: Harth
authors.forename: Dagmar
authors.initials: D
authors.lastname: Grentrup
authors.forename: Thomas
authors.initials: T
authors.lastname: Brüning
authors.forename: Olfert
authors.initials: O
authors.lastname: Landt
authors.forename: Hans
authors.initials: H
authors.lastname: Vetter
authors.forename: Yon-Dschun
authors.initials: YD
authors.lastname: Ko
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001189:Aryl Hydrocarbon Hydroxylases / Q000737:chemistry / Q000235:genetics*; D019363:Cytochrome P-450 CYP1A1 / Q000737:chemistry / Q000235:genetics*; D065633:Cytochrome P-450 CYP1B1; D004247:DNA / Q000737:chemistry / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation / Q000235:genetics / Q000502:physiology; D005858:Germany; D005982:Glutathione Transferase / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D008136:Longevity / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000235:genetics; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics / Q000502:physiology
chemical_list: D004247:DNA; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1; D005982:Glutathione Transferase