Arylamine N-acetyltransferase polymorphisms in Han Chinese patients with ankylosing spondylitis and their correlation to the adverse drug reactions to sulfasalazine.

ABSTRACT

BACKGROUND: Polymorphisms of Arylamine N-acetyltransferase (NAT) that contribute to diverse susceptibilities of some autoimmune diseases are also linked to the metabolism of several drugs including sulfasalazine (SSZ). The aim of this study was to investigate the distribution of NAT polymorphisms in Han Chinese patients with ankylosing spondylitis (AS) and their correlation to sulfasalazine-induced adverse drug reactions (ADRs). METHODS: Arylamine N-acetyltransferase 1 (NAT1) and arylamine N-acetyltransferase 2 (NAT2) genotypes were determined in 266 AS patients who received SSZ treatment and 280 healthy controls. The correlation between NAT polymorphisms and SSZ-induced ADRs was analyzed. RESULTS: The co-occurrence frequency of NAT2 fast acetylator genotype and NAT1*10/NAT1*10 genotype was lower in AS patients than in controls. No positive correlations were detected between NAT polymorphisms and AS clinical features. The prevalence of SSZ-induced ADRs and drug withdrawal was 9.4% and 7.1%, respectively. The frequencies of overall ADRs, dose-related ADRs, and termination of drug treatment because of intolerance were higher in the NAT2 slow acetylator genotype carriers than in the fast-type carriers and in those with co-existence of NAT1 and NAT2 slow acetylator genotypes. Furthermore, the ADRs emerged earlier in the AS cases carrying both NAT1 and NAT2 slow acetylator genotypes. CONCLUSIONS: The prevalence of co-occurring NAT2 fast acetylator genotype and NAT1*10/NAT1*10 genotype was lower in AS patients than in controls. The NAT2 slow acetylator genotype and co-existing NAT1 and NAT2 slow acetylator genotypes appear to be associated with higher risks of SSZ-induced ADRs.