**5. SNPs in the multi-drug resistance 1 gene**

Another of the genes whose mutations may play a role in the pathogenesis of IBD is multi-drug resistance 1 (*MDR1)* gene. *MDR1* encodes P-glycoprotein 170 (P-gp), an ATP-dependent drug transport efflux pump, which highly expressed in many cells and epithelial surfaces, including the epithelium of GI tract [34].

In the gut, P-gp is expressed on the apical surfaces of the superficial columnar epithelial cells in the intestine with the levels of expression gradually rising from the duodenum to the distal parts of the intestine with the highest levels of expression in the distal small bowel and colon [35].

It is now known that substrates for the P-gp pump include a variety of structurally and pharmacologically distinct hydrophobic compounds, such as drugs and toxins, and P-gp might also play a critical role in host bacterial interactions in the gastrointestinal tract and maintenance of intestinal homeostasis [34].

SNPs of *MDR1* can occur naturally in humans, but some of them were related to altered P-gp expression and function. Three most common SNPs that have been repeatedly shown to predict changes in the function of P-gp are synonymous SNPs C1236T (rs1128503) in exon 12 and C3435T (rs1045642) in exon 26 and nonsynonymous, triallelic SNP G2677T/A (Ala893Ser/Thr or rs2032582) located in exon 21. In German, studies have been shown that both T allele and TT genotype of C3435T polymorphism were more frequently present among UC subjects, and the association of G allele of 2677 and IBD was also shown in North American study. However, further research that analyzed different allele combinations of those SNPs in IBD patients gave conflicting results [34].
