Hausmann M, Paul G, Menzel K, Brunner-Ploss R, Falk W, Schölmerich J, Herfarth H, Rogler G
Department of Internal Medicine, University Hospital of Zurich, Switzerland.
Z Gastroenterol. 2008 Mar;46(3):259-65. doi: 10.1055/s-2007-963673.
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.
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.
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 NAT110 allele. 6 % were heterozygous for the NAT13 allele. 6 % were heterozygous for the NAT111 allele. No association was found between NAT1 genotype and clinical response as well as side effects to 5-ASA in patients with UC.
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.
5-氨基水杨酸（5-ASA）在结肠黏膜中由N-乙酰基转移酶1（NAT1）代谢。该酶常见的基因多态性会导致乙酰化速度加快或减慢。5-ASA治疗在高达10%的溃疡性结肠炎（UC）患者中会引起副作用。因此，我们测定了UC患者中NAT1的基因变异，并寻找其与对5-ASA临床反应之间的可能关联。
从78例UC患者中获取DNA。77%的患者在5-ASA治疗期间处于缓解期，而23%患有活动性疾病。使用限制性片段长度多态性（RFLP）和序列分析对23个已知等位基因进行NAT1基因分型。通过查阅病历确定对5-ASA的临床反应，并将其与NAT1基因型相关联。
利用聚合酶链反应（PCR），我们扩增了人类NAT1基因570个碱基对的编码区以及3'非翻译区（UTR）中的240个碱基对。回收了4个先前已知的NAT1等位基因，即NAT13、4、10和11。31%的患者为NAT110等位基因杂合子，4%为纯合子。6%为NAT13等位基因杂合子。6%为NAT1*11等位基因杂合子。在UC患者中，未发现NAT1基因型与临床反应以及对5-ASA的副作用之间存在关联。
NAT1基因型不能预测UC患者对美沙拉嗪的反应或副作用。非基因组效应引起的变异可能与对5-ASA的临床反应相关。
