NAT1 genotypes do not predict response to mesalamine in patients with ulcerative colitis.
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.
Hausmann
M
M
Department of Internal Medicine, University Hospital of Zurich, Switzerland. hausmann@usz.ch
Paul
G
G
Menzel
K
K
Brunner-Ploss
R
R
Falk
W
W
Schölmerich
J
J
Herfarth
H
H
Rogler
G
G
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics / Q000517:prevention & control; D005858:Germany / Q000453:epidemiology; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D019804:Mesalamine / Q000008:administration & dosage*; D017063:Outcome Assessment, Health Care / Q000379:methods* / Q000706:statistics & numerical data; D015995:Prevalence; D016896:Treatment Outcome
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007527:Isoenzymes; D019804:Mesalamine; D001191:Arylamine N-Acetyltransferase; C089384:N-acetyltransferase 1