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MDR1 variants and their functional impact are still being studied intensively. To date, 50 SNP and 3 deletion and insertion mutations has been described [79,80]. g. The most frequent polymorphisms have a character of substitution at position 2677, where guanine usually occurs, or possibly thymine and less frequently, alanine (2677G>T/A). 35 36 Inflammatory Bowel Disease Some authors assume that the reason for the increased transport activity of MDR1 is be‐ cause of this polymorphism . In contrast, mutation 3435C>T in exon 26 is connected with a low expression of P-glycoprotein in the small intestine.
The allelic frequency of the monitored polymorphism in the entire Caucasian population is generally about 11% . The results indicate a possible role of the variant allele of the poly‐ morphism –308G>A in the gene TNFα as a predisposing factor for the onset of IBD. An in‐ creased level of TNFα can lead to a predisposition to a more intense inflammatory reaction and represents one of the risk factors contributing to the development of this disease [49,50]. From the available data it is obvious that genetic factors can determine the IBD character, especially in case of CD.
Nevertheless, this poly‐ morphism somehow influences enzymatic activity and its occurrence correlates with higher levels of thiopurine metabolites. A possible explanation may be the coincidence with an un‐ known polymorphism  or RNA interferency. During the reaction of the catalyzed XDH, free oxygen radicals are generated, which are expected to participate in the hepatotoxic ef‐ fect of thiopurines . 4.
INFLAMMATORY BOWEL DISEASE by Edited by Imre Szabo