Friday 17 February 2006
The human N-acetyltransferase genes NAT1 and NAT2 encode two phase-II enzymes that metabolize various drugs and carcinogens. Functional variability at these genes has been associated with adverse drug reactions and cancer susceptibility.
Mutations in NAT2 leading to the so-called slow-acetylation phenotype reach high frequencies worldwide, which questions the significance of altered acetylation in human adaptation.
NAT2*5B haplotype, which seems to have conferred a selective advantage during the past 6,500 years, exhibits today the strongest association with susceptibility to bladder cancer and adverse drug reactions.
The patterns observed for NAT2 well illustrate how geographically and temporally fluctuating xenobiotic environments may have influenced not only our genome variability but also our present-day susceptibility to disease.
Patin E, Barreiro LB, Sabeti PC, Austerlitz F, Luca F, Sajantila A, Behar DM, Semino O, Sakuntabhai A, Guiso N, Gicquel B, McElreavey K, Harding RM, Heyer E, Quintana-Murci L. Deciphering the ancient and complex evolutionary history of human arylamine N-acetyltransferase genes. Am J Hum Genet. 2006 Mar;78(3):423-36. PMID: 16416399