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Allelic variants of the multidrug resistance gene (MDR1/ABCB1) and response to corticosteroid therapy in patients with inflammatory bowel disease

Background/Aims: Steroid dependency is an important problem in managing patients (pts) with inflammatory bowel disease (IBD). This study examined the association of single nucleotide polymorphisms in the MDR1 of 79 IBD pts (30 ulcerative colitis pts and 49 Crohn' s disease (CD) pts) with respect to response to corticosteroid therapy. Patients and Methods: According to European evidence-based consensus on the diagnosis and management of CD, IBD pts in this study were characterized as steroid-dependent pts (n=47) and good responders to corticosteroids (n=32). Analysis of G2677T polymorphisms in exon 21 and C3435T in exon 26 of MDR1 gene was performed by PCR-RFLP method. Results: Frequencies of the 2677GG, 2677GT and 2677TT MDR1 exon 21 genotypes in the sample were 28, 37 and 14, respectively and of the 3435CC, 3435CT and 3435TT of MDR1 exon 26 genotypes were 17, 40 and 22, respectively. Test result for linkage disequilibrium between loci was found to be significant in good responders (p=0.0002), steroid-dependent pts (p<0.0001) and in total sample (p<0.0001). Pair-wise comparisons of the allele and genotype frequency between good responders and steroid-dependent pts revealed no statistical differences for both loci. Likewise, no statistical differences were found in distributions of the estimated haplotypes between groups. However, subsequent analysis showed G2677/3435T haplotype to be significantly overrepresented in the group of good responders compared to steroid-dependent pts (Hi2= 5.57, p=0.018 ; d.f. =1). There were no confounding effects of age, gender and phenotypes on treatment response. Conclusions: Results in this study indicate that G2677T polymorphisms in exon 21 and C3435T in exon 26 of MDR1 gene don' t have significant influence on development of steroid- dependent disease. However, G2677/3435T haplotype is significantly overrepresented in the group of good responders compared to steroid-dependent pts which means that this haplotype can contribute to response to steroids in IBD pts.

allelic variants; multidrug resistance gene (MDR1/ABCB1)

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