CYP2D6, NAT2 AND CYP2E1 GENETIC POLYMORPHISMS IN NONAGENARIANS

Background: enzymatic polymorphisms affecting the metabolic dispositio n of xenobiotics may modulate the rate of activation or deactivation o f carcinogens and other toxic environmental chemicals. Hence, these po lymorphisms may influence the risk of suffering some types of cancer a nd other degenerative diseases that are incompatible with extreme long evity. Aims: to establish the distribution of three well known enzymat ic polymorphisms that affect the CYP2D6, NAT-2 and CYP2E1 genes and th e activity of their enzymatic gene products, involved in the dispositi on of many xenobiotics, in a group of nonagenarians and in much younge r controls. Patients: the three genotypes were determined in 41, nonag enarians (10 males, mean age 92.2 years, range 90-98) free of known ma lignancies or neurodegenerative diseases. The control groups comprised 217 healthy volunteers (128 males, mean age 36.3 years; SD, 12.7) for the CYP2D6 and NAT2 genotypes and 137 (116 males, mean age 32 years; SD, 18.8) for the CYP2E1 genotype. Methods: after extraction of DNA fr om white blood cells, polymerase chain reaction and restriction fragme nt polymorphism methods were used to identify the allelic variants of the three genotypes. Results: we found no qualitative or quantitative difference in the mutations underlying the three genetic polymorphisms studied, nor in the expected enzymatic phenotypes. Instead, a close p arallelism exists between advanced age and younger groups. Conclusion: longevity does not seem to be related to any special configuration of these three polymorphic traits. Comparisons with younger controls may be adequate when studying the distribution of these polymorphisms in diseases affecting old people. No genetically determined differences i n the activation of drugs metabolized by these enzymes are to be expec ted in very old people.