Lidar Merav, Scherrmann Jean-Michel, Shinar Yael, Chetrit Angela, Niel Elisabeth, Gershoni-Baruch Ruth, Langevitz Pnina, Livneh Avi
Heller Institute of Medical Research, Sheba Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Hashomer, Israel.
Semin Arthritis Rheum. 2004 Feb;33(4):273-82. doi: 10.1053/s0049-0172(03)00137-9.
To identify the ethnic, clinical, genetic, and pharmacokinetic correlates of colchicine treatment failure in patients with familial Mediterranean fever (FMF).
Fifty-nine FMF patients, unresponsive to a daily dose of > or =2 mg colchicine, were compared with 51 colchicine-responsive patients by clinical, demographic, and socioeconomic assessment, FMF gene (MEditerranean FeVer [MEFV]) mutation and serum amyloid A1 (SAA1) gene polymorphism analysis, and plasma and white blood cell colchicine level determination.
Colchicine responders and nonresponders were comparable with respect to gender, age, duration and onset of the disease, and various demographic parameters. The 2 cohorts were found to carry mainly the M694V MEFV mutation and had a similar number of homozygotes or compound heterozygotes. Predominance of the alpha/beta alleles of SAA1 and comparable plasma and polymorphonuclear colchicine concentrations characterized both groups. Nonresponders were from lower socioeconomic backgrounds, had less education, and a more severe form of disease. A statistically significant 2-fold elevation of colchicine concentration in the mononuclear cells (MNC) of responders was found.
Colchicine treatment failure in FMF is associated with inadequate colchicine MNC concentration, probably resulting from a genetic defect unrelated to the underlying FMF.
确定家族性地中海热（FMF）患者中秋水仙碱治疗失败的种族、临床、遗传和药代动力学相关因素。
通过临床、人口统计学和社会经济评估、FMF基因（地中海热[MEFV]）突变和血清淀粉样蛋白A1（SAA1）基因多态性分析，以及血浆和白细胞秋水仙碱水平测定，将59例对每日剂量≥2mg秋水仙碱无反应的FMF患者与51例秋水仙碱反应性患者进行比较。
秋水仙碱反应者和无反应者在性别、年龄、疾病持续时间和发病情况以及各种人口统计学参数方面具有可比性。发现这两个队列主要携带M694V MEFV突变，纯合子或复合杂合子数量相似。两组均以SAA1的α/β等位基因占优势以及血浆和多形核白细胞秋水仙碱浓度相当为特征。无反应者来自社会经济背景较低、受教育程度较低且疾病形式更严重的人群。发现反应者的单核细胞（MNC）中秋水仙碱浓度有统计学意义的2倍升高。
FMF患者中秋水仙碱治疗失败与秋水仙碱在MNC中的浓度不足有关，这可能是由与潜在FMF无关的遗传缺陷导致的。
