Chen Min, Xia Bing, Chen Bixiao, Guo Qiusha, Li Jin, Ye Mei, Hu Zhengguo
Wuhan University Zhongnan Hospital, Wuhan, People's Republic China.
Can J Gastroenterol. 2007 Mar;21(3):155-8. doi: 10.1155/2007/976804.
N-acetyltransferase 2 (NAT2) is an important enzyme catalyzing N-acetylation of sulfasalazine (SASP). The aim of the present study was to investigate associations of the genotypes of NAT2 with inflammatory bowel disease (IBD), and with adverse effects of SASP, which is used as the first-line treatment of IBD.
The wildtype allele (NAT24) and three variant alleles (NAT25B, NAT26A and NAT7B) of the NAT2 gene were determined in 101 patients with IBD (84 patients with ulcerative colitis and 17 patients with Crohn's disease) and 109 healthy controls by the polymerase chain reaction-restriction fragment length polymorphism method. Sixty-eight patients with IBD treated with SASP were followed, and their adverse reactions were recorded.
Eleven patients (16%) experienced adverse effects from SASP, including nine cases of sulfapyridine (SP) dose-related adverse effects and two cases of hypersensitivity (skin rash). Patients with the slow acetylator genotypes without the NAT24 allele experienced adverse effects more frequently (36%) than those with the fast acetylator genotypes with at least one NAT24 allele (11%), but the results were not significantly different (OR of 0.26, 95% CI 0.065 to 1.004; P=0.051). However, those with the slow acetylator genotypes experienced more SP dose-related adverse effects than those with the fast acetylator genotypes (36% versus 8%, OR of 0.17, 95% CI 0.039 to 0.749; P=0.019).
The NAT2 gene polymorphism was not associated with susceptibility to IBD in Chinese populations, but the NAT2 slow acetylator genotypes were significantly associated with SP dose-related adverse effects of SASP in the treatment of IBD.
N-乙酰基转移酶2（NAT2）是催化柳氮磺胺吡啶（SASP）N-乙酰化反应的一种重要酶。本研究旨在探讨NAT2基因多态性与炎症性肠病（IBD）以及与作为IBD一线治疗药物的SASP不良反应之间的关联。
采用聚合酶链反应-限制性片段长度多态性方法，对101例IBD患者（84例溃疡性结肠炎患者和17例克罗恩病患者）及109名健康对照者进行NAT2基因野生型等位基因（NAT24）和3种变异等位基因（NAT25B、NAT26A和NAT7B）的检测。对68例接受SASP治疗的IBD患者进行随访，并记录其不良反应。
11例患者（16%）出现SASP不良反应，其中9例为磺胺吡啶（SP）剂量相关不良反应，2例为超敏反应（皮疹）。无NAT24等位基因的慢乙酰化基因型患者出现不良反应的频率（36%）高于至少有一个NAT24等位基因的快乙酰化基因型患者（11%），但差异无统计学意义（OR为0.26，95%CI为0.065至1.004；P = 0.051）。然而，慢乙酰化基因型患者出现SP剂量相关不良反应的比例高于快乙酰化基因型患者（36%对8%，OR为0.17，95%CI为0.039至0.749；P = 0.019）。
在中国人群中，NAT2基因多态性与IBD易感性无关，但NAT2慢乙酰化基因型与IBD治疗中SASP的SP剂量相关不良反应显著相关。
