ATP-binding cassette transporter ABCG2 (BCRP) and ABCB1 (MDR1) variants are not associated with disease susceptibility, disease phenotype response to medical therapy or need for surgery in Hungarian patients with inflammatory bowel diseases

Fischer, Simon and Lakatos, Péter László and Lakatos, László and Kovács, Ágota and Molnár, Tamás and Altorjay, István and Papp, Mária and Szilvási, Anikó and Tulassay, Zsolt and Osztovits, János and Papp, János and Demeter, Pál and Schwab, Richárd and Tordai, Attila and Andrikovics, Hajnalka (2007) ATP-binding cassette transporter ABCG2 (BCRP) and ABCB1 (MDR1) variants are not associated with disease susceptibility, disease phenotype response to medical therapy or need for surgery in Hungarian patients with inflammatory bowel diseases. Scandinavian Journal of Gastroenterology, 42 (6). pp. 726-733. ISSN 0036-5521

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Abstract

Objective. MDR1 (ABCB1), a member of the ATP- binding cassette (ABC) transporters, is an attractive candidate gene for the pathogenesis of inflammatory bowel diseases (IBD) and perhaps for response to therapy. Since limited data are available on MDR1 and ABCG2 polymorphisms in East European IBD patients, the aim of this study was to investigate ABCG2 and MDR1 variants and responses to medical therapy and/ or disease phenotype in Hungarian patients. Material and methods. A total of 414 unrelated IBD patients (Crohn's disease (CD): 265, age: 35.2 +/- 12.1 years, duration: 8.7 +/- 7.6 years and ulcerative colitis (UC): 149, age: 44.4 +/- 15.4 years, duration: 10.7 +/- 8.9 years) and 149 healthy subjects were investigated. ABCG2 G34A, C421A and MDR1 C3435T, G2677T/A single nucleotide polymorphisms (SNPs) were detected using real- time polymerase chain reaction (PCR). Detailed clinical phenotypes were determined by reviewing the medical charts. Results. The frequency of the ABCG2 and MDR1 SNPs was not significantly different among IBD, CD, UC patients and controls. There was no difference in risk for steroid resistance in CD patients carrying variant ABCG2 (19.6% versus non- carriers 18.4%, p = NS) or MDR1 3435T (CC: 22.2% versus CT/ TT: 17.6%) alleles. In addition, carriage of the variant allele was not associated with disease phenotype, presence of extra-intestinal manifestations, smoking, response to infliximab therapy or the need for surgery. In UC, the carriage of variant ABCG2 alleles seemed to be preventive for arthritis (15.5% versus 31.7%, OR: 0.39, 95% CI: 0.16 - 0.98). Conclusions. MDR1 and ABCG2 SNPs were not associated with disease susceptibility or disease phenotype in Hungarian patients, and variant alleles did not predict the response to medical therapy or the need for surgery. Further studies are needed to clarify the association between the presence of ABCG2 variants and arthritis in UC.

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