Association Between NAT2 Gene Polymorphisms And Side Effects Of Sulfasalazine In Patients With Inflammatory Bowel Disease

Background and Aims N-acetyltransferase 2 (NAT2) gene is highly polymorphic. To date, one allele coding fast acetyltor (wild-type NAT2*4) and several mutated alleles coding for impaired acetylator activity have been identified. Polymorphism of NAT2 gene in humans causes interindividual variations in the metabolism of drugs, arylamines, and potential carcinogens.NAT2 acetylation polymorphisms have been shown to link to susceptibility to certain autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, and Behcet's disease, but have not been studied for IBD. The patients with rheumatoid arthritis with the slow NAT2 acetylator genotypes have been shown to have more side effects than fast acetylator genotypes when taking SASP.The present study is aimed to investigate the possible role of NAT2 gene polymorphism in susceptibility to inflammatory bowel disease (IBD) in Chinese patients and the association between NAT2 slow acetylator genotype and the side effects of SASP in treatment of the patients.Methods Three point mutants (C481T, G590A and G857A) in the NAT2 were genotyped in 101 patients with IBD (UC 84 and CD 17) and 109 healthy controls by polymerase chain reaction- restriction fragment length polymorphism techniques. Sixty-eight patients of IBD treated with SASP were followed and recorded side effects of SASP and analyzed for an association between the NAT2 slow acetylator genotype and the side effects.Result The frequency of NAT2 alleles and acetylator genotypes in IBD patients were not different significantly from the healthy controls. The NAT2 slow acetylator genotypes of IBD patients had experienced side effects more frequently than the rapid acetylator genotypes of IBD patients in SASP treatment, but the result is not statistically significance .(36% vs 11%, OR=0.26, 95%CI=0.065~1.004, P=0.051). However, theslow acetylator genotypes of IBD patients had experienced much more frequent of SP concentration-related side effects than the rapid acetylator genotypes (36% vs 8%,OR=0.17, 95%CI=0.039~0.749, P=0.019).Conclusions the NAT2 genetic polymorphism was not associated with susceptibility to IBD in Chinese populations. The NAT2 slow acetylator genotypes were not associated with the side effects of S ASP, but significantly associated with serum SP concentration-related side effects in the treatment of IBD.