N-acetyltransferase 2 (Nat2) polymorphism in the sand rat Psammomys obesus.

Human arylamine N-acetyltransferase 1 (NAT1) and its homologue in rodents (Nat2) are polymorphic xenobiotic metabolizing enzymes and also seem to play a role in endogenous metabolism. NAT1 and Nat2 polymorphism was associated to cancers under xenobiotic procarcinogens metabolism as well as under endogenous substrate metabolism. This study investigated the p-aminobenzoic acid (PABA) -Nat2 catalytic activity and its polymorphism in liver homogenates of adult sand rats Psammomys obesus Cretzschmar, 1828. These Saharian sand rats develop high incidence of spontaneous cancers under standard laboratory diet. The average value of PABA-Nat2 specific activity tested in nine sand rats was significant (2.96 ± 2.16 nmoles/min/mg). The N-acetylation exhibited a bimodal distribution. There was a significant difference (p<0.01) between PABA-Nat2 activity in the fast acetylators group (4.10 ± 1.67 nmol/min/mg) and slow acetylators group (0.7 ± 0.27 nmol/min/mg). The percentage of the fast acetylator group was 66.66%. These results support the presence of Nat2 polymorphism in the liver of the strain sand rats Psammomys obesus. This strain is useful for investigating the role of Nat2 polymorphisms in susceptibility to cancers related to arylamine carcinogen exposures as well as to endogenous substrate metabolism.

Polymorphisms in NAT2 gene and atherosclerosis in an Algerian population.

BACKGROUND AND AIMS: The etiology of atherosclerosis is multifactorial. Genetic and environmental factors are involved in the development of atherosclerosis. Human arylamine N-acetyltransferase 2 (NAT2) is an important metabolizing enzyme that exhibits genetic polymorphisms and modifies individual response and/or toxicity to many xenobiotics. We undertook this study to investigate the NAT2 polymorphisms in patients with atherosclerosis. METHODS: Genotyping for NAT2 alleles was performed using polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) in 285 Algerian patients with atherosclerosis and 286 controls. RESULTS: There was no association between NAT2 polymorphisms and atherosclerosis risk. However, the haplotype NAT2(*)5F decreased susceptibility to the disease (p = 0.005, OR = 0.55, 95% CI = 0.37-0.84). The frequency of the slow acetylator phenotype was approximately 50% in both cases and controls. CONCLUSIONS: These results suggest that NAT2 polymorphisms may not be involved in the pathogenesis of atherosclerosis.