Cytochrome p450 (cyp450,2d6*a), n-acetyltransferase-2 (nat2*7, a) and multidrug resistance 1 (mdr1 3435 t) alleles collectively increase risk of ulcerative colitis

Farzane Lotfi,1,* Asad vaisi-raygani ,2

1. Kermanshah University of Medical Sciences
2. Kermanshah University of Medical Sciences



Discovering the association between genetic variations of metabolizing enzymes with idiopathic diseases such as ulcerative colitis (uc) may not only be an auxiliary agent in diagnosis, but also an effective pharmacotherapy for inflammatory bowel disease (ibd). the aim of present case-control study was to determine the association of cytochrome p450 2d6 (cyp2d6 *4), n- acteyltransferase-2 nat2*7 and multidrug resistance 1 (mdr1) 3435 c/t genotypes with uc susceptibility and tpmt enzyme activity.


Tpmt activity was measured by hplc and genotypes for the three mentioned polymorphisms were determined in 215 unrelated uc patients and 212 unrelated healthy controls by pcr-rflp in kurdish population from iran.


Cyp2d6*4 a allele, nat2*7 a and mdr1 3435 c/t alleles act synergistically to increase the risk of uc by 3.49 times. the frequency of a allele of cyp2d6*4 was significantly higher in uc patients (12.6%) in compared to control subjects (8.5%, p=0.046) and significantly increased the risk of uc by 1.56 fold. the frequencies of nat2*7 genotypes and alleles were similar in both studied groups.


The most important outcome of this study for the first time demonstrated that the simultaneous presence of t mdr1, a cyp2d6*4 and a nat2*7 alleles robustly increases the risk of developing uc by 3.49 fold. current study suggests that cyp2d6*4 and mdr1 3435 c/t gene polymorphisms may be risk factor for uc susceptibility.


Mdr, cytochrome p450, nat 2, tpmt, uc