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NAT1 genotypes do not predict response to mesalamine in patients with ulcerative colitis


Hausmann, M; Paul, G; Menzel, K; Brunner-Ploss, R; Falk, W; Schölmerich, J; Herfarth, H; Rogler, G (2008). NAT1 genotypes do not predict response to mesalamine in patients with ulcerative colitis. Zeitschrift für Gastroenterologie, 46(3):259-265.

Abstract

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.

Abstract

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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Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Gastroenterology and Hepatology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:March 2008
Deposited On:23 Dec 2008 12:11
Last Modified:05 Apr 2016 12:45
Publisher:Thieme
ISSN:0044-2771
Additional Information:Copyright: Georg Thieme Verlag. Full text at http://www.thieme-connect.de/ejournals/pdf/zfg/doi/10.1055/s-2007-963673.pdf
Publisher DOI:https://doi.org/10.1055/s-2007-963673
PubMed ID:18322880

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