Zusammenfassung
Background: 5-Aminosalicylic acid (5-ASA) is metabolised in colonic mucosa by N-acetyltransferase 1 (NAT1). Common genetic polymorphisms in this enzyme result in rapid or slow acetylation. 5-ASA treatment causes side effects in up to 10% of patients with ulcerative colitis (UC). We therefore determined genetic variations of NAT1 in patients with UC and looked for a possible association with the ...
Zusammenfassung
Background: 5-Aminosalicylic acid (5-ASA) is metabolised in colonic mucosa by N-acetyltransferase 1 (NAT1). Common genetic polymorphisms in this enzyme result in rapid or slow acetylation. 5-ASA treatment causes side effects in up to 10% of patients with ulcerative colitis (UC). We therefore determined genetic variations of NAT1 in patients with UC and looked for a possible association with the clinical response to 5-ASA. Methods: DNA was obtained from 78 patients with UC. 77% of the patients were in remission during 5-ASA treatment, whereas 23% suffered from active disease. NAT1 genotyping was performed for 23 known alleles using RFLP and sequence analysis. Clinical response to 5-ASA was determined by medical record review and associated with NAT1 genotypes. Results: Utilising PCR we amplified a 570-bp coding region of the human NAT1 gene in addition to 240 bp in the 3'-untranslated region (UTR). 4 NAT1 alleles previously known as NAT1 *3, *4, *10 and *11 were recovered. 31% of the patients were heterozygous and 4% homozygous for the NAT1*10 allele. 6% were heterozygous for the NAT1*3 allele. 6% were heterozygous for the NAT1*11 allele. No association was found between NAT1 genotype and clinical response as well as side effects to 5-ASA in patients with UC. Conclusions: NAT1 genotypes do not predict response or side effects to mesalamine in patients with UC. Variations caused by non-genomic effects may be associated with the clinical response to 5-ASA.
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