Multidrug Resistance 1 Gene Polymorphisms in Inflammatory Bowel Disease

Abstract

Inflammatory bowel disease (IBD) is a collection of inflammatory diseases affecting the GIT. It seems to be caused by dysregulated immune response to commensal intestinal bacteria, triggered by a combination of genetic and environmental factors. MDR1 gene, located on chromosome 7, encodes the membrane transport protein P-glycoprotein (P-gp), which has been proposed to be closely related to bowel diseases. P-glycoprotein acts as an ATP-dependent efflux transporter pump and plays an important role in drug disposition and response. In this regard the present study aimed to investigate the most common three SNPs of MDR1 gene (C3435T, G2677T and C1236T) in IBD patients and to study their association with disease severity, prognosis and response to treatment. For this purpose, samples were collected from 60 IBD patients (Group I) recruited from IBD clinic of Tropical Medicine Department at Ain Shams University Hospitals and 50 age and sex- matched apparently healthy controls (Group II). IBD patients were diagnosed according to clinical, endoscopic and histopathological examination. They were 50 UC and 10 CD patients Ulcerative colitis patients were subclassified according to Truelove and Witts’ severity score into mild, moderate and severe UC patients. IBD patients were also subdivided according to GCs response into glucocorticoid responders and glucocorticoid non-responders. All individuals in the study were subjected to full history including present history, family history and past history, general clinical examination, biopsy for site of disease determination by sigmoidoscopy or full colonoscopy for IBD patients only, general laboratory investigations including CBC, serum sodium, potassium and albumin, CRP and ESR and assay of MDR1 gene SNPs (C3435T, G2677T and C1236T) by PCR amplification and restriction analysis.