Beyeler C, Daly A K, Armstrong M, Astbury C, Bird H A, Idle J R
Clinical Pharmacology Unit, Royal Bath Hospital, Harrogate, United Kingdom.
J Rheumatol. 1994 Jun;21(6):1034-9.
To determine whether particular genotypes for the cytochrome P450 enzyme CYP2D6, a polymorphic enzyme, are associated with susceptibility to rheumatoid arthritis (RA) and whether CYP2D6 enzyme activity is altered as a result of the disease or its treatment.
CYP2D6 genotypes and metabolic phenotypes were determined for 53 patients with RA and 73 healthy controls. Genotyping was carried out by restriction fragment length polymorphism analysis with the restriction enzyme XbaI and by 2 separate polymerase chain reaction assays; phenotyping was by analysis of in vivo metabolism of the probe drug debrisoquin.
No significant difference in the distribution of overall genotypes between the 2 groups was observed. When the frequency of individual alleles was investigated, a significant difference in allele frequency for the CYP2D6D allele (p < 0.005) was observed with fewer patients with RA showing this mutation. Metabolic phenotypes were broadly similar between the patients and controls. However, a number of the patients with RA showed higher than expected metabolic ratios for their particular genotype due to interference by the analgesic dextropropoxyphene in the phenotyping procedure.
Our findings demonstrate that CYP2D6 activity is not impaired in RA.
确定细胞色素P450酶CYP2D6（一种多态性酶）的特定基因型是否与类风湿关节炎（RA）易感性相关，以及CYP2D6酶活性是否因该疾病或其治疗而改变。
测定了53例RA患者和73例健康对照者的CYP2D6基因型和代谢表型。采用限制性内切酶XbaI通过限制性片段长度多态性分析和2种独立的聚合酶链反应检测进行基因分型；通过分析探针药物异喹胍的体内代谢进行表型分析。
两组间总体基因型分布无显著差异。在研究单个等位基因频率时，观察到CYP2D6D等位基因频率存在显著差异（p < 0.005），显示该突变的RA患者较少。患者和对照者的代谢表型大致相似。然而，由于表型分析过程中镇痛药右丙氧芬的干扰，一些RA患者的特定基因型代谢率高于预期。
我们的研究结果表明，RA患者的CYP2D6活性未受损。
