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Copyright ©2006 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Jun 21, 2006; 12(23): 3636-3644
Published online Jun 21, 2006. doi: 10.3748/wjg.v12.i23.3636
Multidrug resistance 1 gene in inflammatory bowel disease: A meta-analysis
V Annese, MR Valvano, O Palmieri, A Latiano, F Bossa, A Andriulli
V Annese, MR Valvano, O Palmieri, A Latiano, F Bossa, A Andriulli, Unità di Gastroenterologia, Ospedale IRCCS “Casa Sollievo della Sofferenza”. San Giovanni Rotondo (Fg), Italy
Supported by a grant from the Health Minister of Health N° RF03GA01, RC0503GA20
Correspondence to: Vito Annese, MD, UO Gastroenterologia Ospedale IRCCS “Casa Sollievo della Sofferenza”. Viale Cappuccini, 1-71013 S. Giovanni Rotondo, Italy. v.annese@operapadrepio.it
Telephone: +39-882-410335  Fax: +39-882-411879
Received: February 24, 2006
Revised: February 28, 2006
Accepted: April 16, 2006
Published online: June 21, 2006
Abstract

The MDR1 gene is an attractive candidate gene for the pathogenesis of inflammatory bowel disease (IBD) and perhaps response to therapy, with evidences at both functional and genetic levels. Its product, the P-glycoprotein (P-gp) functions as a transmembrane efflux pump thus influencing disposition and response of many drugs, some of whom (i.e. glucocorticoids) central to IBD therapy. In addition P-gp is highly expressed in many epithelial surfaces, included gastrointestinal tract (G-I) with a putative role in decreasing the absorption of endogenous or exogenous toxins, and perhaps host-bacteria interaction. Many genetic variations of MDR1 gene has been described and in some instances evidences for different P-gp expression as well drugs metabolism have been provided. However data are often conflicting due to genetic heterogeneity and different methodologies employed. Perhaps the greatest piece of evidence of the physiological importance of P-gp in the G-I tract has come from the description of the mdr1 knock-out mice model, which develops a spontaneous colitis in a specific pathogen-free environment. Studies investigating MDR1 gene polymorphism and predisposition to IBD have also shown conflicting results, owing to the known difficulties in complex diseases, especially when the supposed genetic contribution is weak. In this study we have undertaken a meta-analysis of the available findings obtained with two SNPs polymorphism (C3435T and G2677T/A) in IBD; a significant association of 3435T allele and 3435TT genotype has been found with UC (OR = 1.17, P = 0.003 and OR = 1.36, P = 0.017, respectively). In contrast no association with CD and the G2677T/A polymorphism could be demonstrated.

Keywords: Inflammatory bowel disease, Ulcerative colitis, Crohn’s disease, P-glycoprotein, Multidrug resistance 1 gene, Meta-analysis