Bohanec Grabar Petra, Rozman Blaz, Tomsic Matija, Suput Dasa, Logar Dusan, Dolzan Vita
Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
Eur J Clin Pharmacol. 2008 Sep;64(9):871-6. doi: 10.1007/s00228-008-0498-2. Epub 2008 May 22.
Leflunomide is a disease-modifying antirheumatic drug used for treating rheumatoid arthritis (RA). In vitro studies demonstrated that cytochromes P450 (CYPs), mainly CYP1A2 and CYP2C19, might be involved in leflunomide activation. The aim of our study was to investigate whether genetic polymorphisms of CYP1A2, CYP2C19, and CYP2C9 influence leflunomide toxicity.
A genotyping approach was used to determine CYP1A21F, CYP2C192, CYP2C1917, CYP2C92, and CYP2C9*3 alleles in 105 RA patients.
Leflunomide treatment was well tolerated by 62 patients, whereas 43 patients discontinued the treatment within the first year due to toxicity. Patients with CYP1A21F CC genotype had a 9.7-fold higher risk for overall leflunomide-induced toxicity than did the carriers of CYP1A21F A allele [P = 0.002, odds ratio = 9.708, 95% confidence interval = 2.276-41.403]. No significant association between the CYP2C19 and CYP2C9 genotypes and the leflunomide toxicity was observed.
Our results suggest that the CYP1A2*1F allele may be associated with leflunomide toxicity in RA patients.
来氟米特是一种用于治疗类风湿关节炎（RA）的改善病情抗风湿药。体外研究表明，细胞色素P450（CYPs），主要是CYP1A2和CYP2C19，可能参与来氟米特的活化。我们研究的目的是调查CYP1A2、CYP2C19和CYP2C9的基因多态性是否会影响来氟米特的毒性。
采用基因分型方法测定105例RA患者的CYP1A21F、CYP2C192、CYP2C1917、CYP2C92和CYP2C9*3等位基因。
62例患者对来氟米特治疗耐受性良好，而43例患者因毒性在第一年就停止了治疗。CYP1A21F CC基因型患者发生来氟米特总体毒性的风险比CYP1A21F A等位基因携带者高9.7倍[P = 0.002，比值比 = 9.708，95%置信区间 = 2.276–41.403]。未观察到CYP2C19和CYP2C9基因型与来氟米特毒性之间存在显著关联。
我们的结果表明，CYP1A2*1F等位基因可能与RA患者的来氟米特毒性有关。
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