Polymorphic metabolic susceptibility genes and longevity: a study in octogonarians.
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.
Pesch
Beate
B
Berufsgenossenschaftliches Forschungsinstitut für Arbeitsmedizin, Ruhr-Universität Bochum, Bürkle-de-la-Camp-Platz 1, Bochum D-44789, Germany.
Düsing
Rainer
R
Rabstein
Sylvia
S
Harth
Volker
V
Grentrup
Dagmar
D
Brüning
Thomas
T
Landt
Olfert
O
Vetter
Hans
H
Ko
Yon-Dschun
YD
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
D004247:DNA; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1; D005982:Glutathione Transferase