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

Laboratorio Epidemiologico, Ospedale Policlinico IRCCS, Milan, Italy; Institute of Internal Medicine, University of Milan, Milan, Italy; Italian National Research Centers on Aging, INRCA, Ancona, Italy; Department of Experimental Pathology, University of Bologna, Bologna, Italy; Department of Experimental Pathology and Oncology, University of Florence, Florence, Italy; Atherosclerosis Prevention Centre, Department of Internal Medicine, University of Genoa, Genoa, Italy; Genetics Research Insitute, Strada della Carità 10, 20135, Milan, Italy
Biochemical and Biophysical Research Communications (Impact Factor: 2.28). 03/2001; DOI: 10.1006/bbrc.2001.4280

ABSTRACT 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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