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Polymorphisms in multidrug resistance 1 (MDR1) gene are associated with refractory Crohn disease and ulcerative colitis

Genes & Immunity volume 5, pages 530–539 (2004)Cite this article

Abstract

We used coding and noncoding polymorphisms evenly spaced across the ABCB1/MDR1 gene to perform association analysis in Slovenian patients with inflammatory bowel diseases and to obtain haplotype structure and patterns of linkage disequilibrium (LD) in the MDR1 gene. A disease association study was performed in 307 IBD patients, including 144 patients with ulcerative colitis (UC) and 163 patients with Crohn's disease (CD), and 355 healthy controls. Here we report an association between MDR1 alleles, polymorphisms and haplotypes and refractory CD patients, who do not respond to standard therapy, including patients who develop fistulas. We also report an association with UC and MDR1 polymorphisms in a Slovenian population. Haplotypes significantly associated with diseases were defined by single-nucleotide polymorphisms (SNPs) in exons 12 (1236 C>A), 21(A893S), and 26 (3435 C>T). In addition, two intronic SNPs in LD with the disease haplotype, one in intron 13 (rs2235035) and another in intron 16 (rs1922242), were significantly associated with refractory Crohn (P=0.026, odds ratio (OR) 2.7 and P=0.025, OR 2.8, respectively), as well as with UC (P=0.006, OR 1.8 and P=0.026, OR 1.9, respectively). Our results suggest that MDR1 is a potential target for therapy in refractory CD patients and in patients with UC.

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Acknowledgements

The Ministry of Education, Science and Sport of Republic of Slovenia supported this study (Grant number: Z3-6028-0381-04). Ethical Committee of the Republic of Slovenia in February 2000 agreed the scope of the study. We thank Dr Anton Cerar for providing us with the patients' tissue biopsies. We are grateful to patients who participated in the study. We also thank Teo Žižek for excellent technical assistance.

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Authors and Affiliations

  1. Laboratory of Molecular Genetics, Institute of Pathology, Medical Faculty, Ljubljana, Slovenia

    U Potočnik & D Glavač

  2. Division of Internal Medicine, Department of Gastroenterology, University Medical Centre, Ljubljana, Slovenia

    I Ferkolj

  3. Laboratory of Genomic Diversity, National Cancer Institute, Frederick, MD, USA

    U Potočnik & M Dean

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  1. U Potočnik
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Correspondence to M Dean.

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Potočnik, U., Ferkolj, I., Glavač, D. et al. Polymorphisms in multidrug resistance 1 (MDR1) gene are associated with refractory Crohn disease and ulcerative colitis. Genes Immun 5, 530–539 (2004). https://doi.org/10.1038/sj.gene.6364123

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