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Is there evidence to claim or deny association between variants of the multidrug resistance gene (MDR1 or ABCB1) and inflammatory bowel disease?

Authors

  • Elias Zintzaras PhD

    Corresponding author
    1. Department of Biomathematics, University of Thessaly School of Medicine, Larissa, Greece, and Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts
    • Department of Biomathematics, University of Thessaly School of Medicine, 2 Panepistimiou Str, Larissa 41110, Greece
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Abstract

Background:

Inflammatory bowel disease (IBD) is a complex disease with a genetic background. Crohn's disease (CD) and ulcerative colitis (UC) are the two main types of IBD. There is indication that variants in the MDR1 gene are associated with development of IBD. However, the 20 published genetic association studies (GAS) for the three most popular variants in the MDR1 gene (C3435T, G2677T/A, and C1236T) have produced inclusive results.

Methods:

In order to decrease the uncertainty of pooled risk effects and to explore the trend and stability of the risk effects, a meticulous meta-analysis, including cumulative and recursive cumulative meta-analysis, of the GAS related to the MDR1 gene with susceptibility to IBD was conducted. The risk effects were estimated based on the odds ratio (OR) of the allele contrast and the generalized odds ratio (ORG).

Results:

The analysis showed marginal significant association for the C3435T variant in UC: the risk estimate for the allele contrast was OR = 1.11 (1.00–1.22) and ORG = 1.12 (1.01–1.27), indicating that a subject with high mutational load has a 12% higher probability of being diseased. The respective cumulative meta-analysis indicated a downward trend of association, as evidence accumulates with the association being significant during the whole published period. The cumulative meta-analysis for the other variants showed lack of any trend of association. However, the recursive cumulative meta-analysis showed that there is no sufficient evidence for denying or claiming an association for all variants.

Conclusions:

More evidence is needed to draw safe conclusions regarding the association of MDR1 variants and development of IBD. (Inflamm Bowel Dis 2012;)

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