Association of Drug Transporter Gene ABCB1 (MDR1) 3435C to T Polymorphism with Colchicine Response in Familial Mediterranean Fever

ABDURRAHMAN TUFAN, MELIH O. BABAOGLU, ALI AKDOGAN, UMIT YASAR, MERAL CALGUNERI, UMUT KALYONCU, OMER KARADAG, MUTLU HAYRAN, A. IHSAN ERTENLI, ATILA BOZKURT, and SEDAT KIRAZ

ABSTRACT.

Objective. 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.

Methods. Patients (n = 120) were examined for colchicine responses. ABCB1 gene 3435C to T genotypes were determined to analyze associations with colchicine resistance.

Results. 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).

Conclusion. 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. (First Release June 15 2007; J Rheumatol 2007;34:1540-4)

Key Indexing Terms:

FAMILIAL MEDITERRANEAN FEVER
COLCHICINE
ABCB1 POLYMORPHISM
MDR1
PHARMACOGENETICS

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From the Division of Rheumatology, Department of Internal Medicine, Department of Pharmacology, and Division of Oncology, Department of Internal Medicine, Hacettepe University Faculty of Medicine, Ankara, Turkey.

Supported by grants from the Scientific and Technical Research Council of Turkey (SBAG-COST B25) and the Association of Rheumatological Research and Education of Turkey. Dr. Yasar has been supported by the Turkish Academy of Science, Young Scientist Award Program (UY/TUBA-GEBIP/2005-17).

A. Tufan, MD, Medical Specialist, Internal Medicine; A. Akdogan, MD, Medical Specialist, Rheumatology; M. Calguneri, MD, Professor of Internal Medicine and Rheumatology; U. Kalyoncu, MD, Fellow of Rheumatology; O. Karadag, MD, Fellow of Rheumatology; I. Ertenli, MD, Professor of Internal Medicine and Rheumatology; S. Kiraz, MD, Professor of Internal Medicine and Rheumatology, Division of Rheumatology; M.O. Babaoglu, MD, Associate Professor of Pharmacology; U. Yasar, MD, Associate Professor of Pharmacology; A. Bozkurt, MD, PhD, Professor of Pharmacology, Department of Pharmacology; M. Hayran, MD, PhD, Associate Professor of Oncology, Division of Oncology.

Address reprint requests to Dr. A. Tufan, Department of Internal Medicine, Division of Rheumatology, Hacettepe University Faculty of Medicine, TR-06100, Sihhiye, Ankara, Turkey. E-mail: tufan@hacettepe.edu.tr

Accepted for publication March 19, 2007.

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