Tanaka Eiichi, Taniguchi Atsuo, Urano Wako, Nakajima Hiroshi, Matsuda Yuko, Kitamura Yutaka, Saito Masayuki, Yamanaka Hisashi, Saito Terunobu, Kamatani Naoyuki
Institute of Rheumatology and Division of Statistical Genetics, Tokyo Women's Medical University, Japan.
J Rheumatol. 2002 Dec;29(12):2492-9.
N-acetyltransferase 2 (NAT2) is a key enzyme for the acetylation of sulfasalazine (SSZ). We examine whether there was a correlation between diplotype configurations (combinations of 2 haplotypes for a subject) at the NAT2 gene and the adverse effects of SSZ used for the treatment of rheumatoid arthritis (RA).
The findings from 144 patients with RA who had been treated with SSZ were collected from our outpatient department and used for a retrospective study. Haplotype analysis was performed by the maximum-likelihood estimation based on the EM algorithm using the obtained polymorphism data.
Sixteen patients (11.1%) had experienced adverse effects from SSZ, the most common being allergic reactions including rash and fever. The slow acetylators who had no NAT24 haplotype had experienced adverse effects more frequently (62.5%) than the fast acetylators who had at least one NAT24 haplotype (8.1%) (p < 0.001, OR 7.73, 95% CI 3.54-16.86). In 25% of the slow acetylators, the adverse effects were so severe that they were hospitalized.
Genotyping the NAT2 gene followed by estimation of diplotype configuration before administration of SSZ is likely to reduce the frequency of adverse effects in Japanese patients with RA.
N - 乙酰转移酶2（NAT2）是柳氮磺胺吡啶（SSZ）乙酰化的关键酶。我们研究NAT2基因双倍型构型（个体的2个单倍型组合）与用于治疗类风湿关节炎（RA）的SSZ不良反应之间是否存在相关性。
从我们的门诊收集144例接受过SSZ治疗的RA患者的资料用于回顾性研究。使用获得的多态性数据，通过基于期望最大化（EM）算法的最大似然估计进行单倍型分析。
16例患者（11.1%）出现了SSZ的不良反应，最常见的是包括皮疹和发热在内的过敏反应。没有NAT2 * 4单倍型的慢乙酰化者出现不良反应的频率（62.5%）高于至少有一个NAT2 * 4单倍型的快乙酰化者（8.1%）（p < 0.001，比值比7.73，95%置信区间3.54 - 16.86）。25%的慢乙酰化者不良反应严重到需要住院治疗。
在日本RA患者中，在给予SSZ之前对NAT2基因进行基因分型并估计双倍型构型可能会降低不良反应的发生率。
