Polymorphisms of Drug-Metabolizing Enzymes in Healthy Nonagenarians and Centenarians: Difference at GSTT1 Locus

Department of Experimental Pathology and Oncology, University of Florence, Florence, Italy
Biochemical and Biophysical Research Communications (Impact Factor: 2.3). 03/2001; 280(5):1389-1392. DOI: 10.1006/bbrc.2001.4280


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.

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Available from: Stefano Bertolini, Dec 25, 2013
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    • "Identification of genuine aging genes may uncover " master genes " that increase our understanding of many age-related diseases. There are a number of biological pathways that have been reported important in human aging, including lipid/cholesterol metabolism [GO:0006629; GO:0008203] (APOE, PON1, CETP) (Barzilai et al., 2003; de Chaves and Narayanaswami, 2008; Efrat and Aviram, 2010), immune system processes [GO:0002376] (IL6 and IL10) (Jylhävä and Hurme, 2009), drug metabolism [KEGG:hsa00982] (GSTT1) (Glatt et al., 2007; Taioli et al., 2001), energy metabolism in mitochondria (SIRT3) (Polito et al., 2010), and insulin receptor signaling pathway [GO:0008286] (IGF1R, FOXO3A, KLOTHO) (Arking et al., 2005; Suh et al., 2008; Willcox et al., 2008). Insights into human aging have been gained from studying model organisms. "
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