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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.

bmc pharmacology and toxicology

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