Tufan Abdurrahman, Babaoglu Melih O, Akdogan Ali, Yasar Umit, Calguneri Meral, Kalyoncu Umut, Karadag Omer, Hayran Mutlu, Ertenli A Ihsan, Bozkurt Atila, Kiraz Sedat
Division of Rheumatology, Department of Internal Medicine, Hacettepe University Faculty of Medicine, Sihhiye, Ankara, Turkey.
J Rheumatol. 2007 Jul;34(7):1540-4. Epub 2007 Jun 15.
Colchicine is a mainstay of treatment in familial Mediterranean fever (FMF); however, 5%-10% of patients do not respond to colchicine. Adenosine triphosphate-binding cassette subfamily B member 1 (ABCB1 or MDR1) is a drug transporter that extrudes colchicine out of cells. ABCB1 gene 3435C to T polymorphism has been demonstrated to alter MDR1 expression in mononuclear cells. Thus, the amount of MDR1 in mononuclear cells may alter response to colchicine. We investigated the association between MDR1 3435C to T polymorphism and colchicine response in patients with FMF.
Patients (n = 120) were examined for colchicine responses. ABCB1 gene 3435C to T genotypes were determined to analyze associations with colchicine resistance.
Ninety-eight patients were evaluated as responders and 22 as nonresponders. The distributions of ABCB1 CC, CT, and TT genotypes were significantly different between responsive and nonresponsive groups (chi-square = 6.86, p = 0.032). Colchicine resistance was significantly higher in patients harboring the C allele than in patients with TT genotype (odds ratio 9.71, 95% CI 1.58-58.76). Similarly, the mean colchicine dose to prevent remission was significantly lower in the TT group compared with subjects with the C allele (p = 0.014).
Our study revealed an association between 3435C to T polymorphism and colchicine response in patients with FMF. Patients with the TT genotype for the ABCB1 3435C to T variant responded better to colchicine in terms of treatment efficacy and colchicine dose requirements.
秋水仙碱是家族性地中海热（FMF）治疗的主要药物；然而，5%-10%的患者对秋水仙碱无反应。三磷酸腺苷结合盒亚家族B成员1（ABCB1或MDR1）是一种药物转运蛋白，可将秋水仙碱排出细胞外。已证实ABCB1基因3435C→T多态性可改变单核细胞中MDR1的表达。因此，单核细胞中MDR1的量可能会改变对秋水仙碱的反应。我们研究了FMF患者中MDR1 3435C→T多态性与秋水仙碱反应之间的关联。
对120例患者进行秋水仙碱反应检查。确定ABCB1基因3435C→T基因型，以分析与秋水仙碱耐药性的关联。
98例患者被评估为反应者，22例为无反应者。反应组和无反应组之间ABCB1 CC、CT和TT基因型的分布有显著差异（卡方=6.86，p=0.032）。携带C等位基因的患者秋水仙碱耐药性显著高于TT基因型患者（比值比9.71，95%可信区间1.58-58.76）。同样，与携带C等位基因的受试者相比，TT组预防缓解的秋水仙碱平均剂量显著更低（p=0.014）。
我们的研究揭示了FMF患者中3435C→T多态性与秋水仙碱反应之间的关联。ABCB1 3435C→T变体的TT基因型患者在治疗效果和秋水仙碱剂量需求方面对秋水仙碱反应更好。
