Multidrug resistance Gene-1 polymorphisms (C3435T and G2677T) and the risk of inflammatory bowel disease in Egyptian patients

Inflammatory bowel disease (IBD) is a gastrointestinal inflammatory illness that is chronic and recurrent in nature. IBD is thought to be induced by excessive cell-mediated immune response to the gut microbiota in genetically predisposed individuals [1], [2]. Ulcerative colitis (UC) and Crohn’s disease (CD) are two of the most well-known inflammatory bowel diseases that share some symptoms together. Both diseases are affected by genetic susceptibility [3].

Some genes as the multidrug resistance 1 (MDR1) gene which plays a role in protecting cells against xenobiotics, toxins, and their metabolites [4], were found to play a role in IBD development [5]. MDR 1 gene is an ATP-binding cassette, subfamily B 1 gene (ABCB1), which is a highly conserved candidate gene encoding a 170 kDa transmembrane protein pump termed P-glycoprotein (Pgp). Pgp is a transport protein that is one of the ATP-binding cassette superfamily (ABC family) [6], [7]. Pgp is highly expressed in the apical surfaces of superficial columnar epithelial cells in the intestine, with levels steadily increasing from the duodenum to the distal intestine, with the distal small bowel and colon expressing the most. Although its physiological function in the gut is unknown, its high expression levels imply that it may play a role in not only guarding against xenobiotics, but also in influencing host-bacterial interactions [8].

Numerous studies have examined the links between two of the most frequently occurring SNPs, C3435T (Exon 26, rs1045642) and G2677T/A (Exon 21, rs2032582), and illness development and drug response in various groups [9]. Patients with UC are more likely to have the C3435T MDR1 and G2677T/A polymorphisms, which are related with decreased intestinal Pgp expression [10].

Apparently, there is uncertainty concerning the role of C3435T and G2677T polymorphisms in IBD pathogenesis due to conflicting results of the studies in different populations; hence we aimed to examine the relationship between the MDR-1 gene (C3435T) & (G2677T/A) polymorphism and IBD together with evaluation their prevalence in Egyptian patients.

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