Home Current Issue Previous Issues Published Ahead-of-Print For Authors Journal Info
Skip Navigation LinksHome > July 2013 - Volume 19 - Issue 8 > Thiopurine Effectiveness in Patients with Crohn's Disease:...
Inflammatory Bowel Diseases:
doi: 10.1097/MIB.0b013e31828828d3
Original Clinical Articles

Thiopurine Effectiveness in Patients with Crohn's Disease: A Study of Genetic and Clinical Predictive Factors

Koifman, Eduard MD*; Karban, Amir MD*,†; Mazor, Yoav MD*; Chermesh, Irit MD*,†; Waterman, Matti MD*,†; Almog, Ronit MD, PhD; Ben-Horin, Shomron MD§; Eliakim, Rami MD§; Krivoy, Norberto MD†,‖; Efrati, Edna PhD‖,¶; Chowers, Yehuda MD*,†

Collapse Box

Abstract

Background:

Thiopurines are efficacious in the treatment of Crohn's disease and were recently shown to induce T-cell apoptosis by modulation of Rac1 activation. To assess whether polymorphisms in Rac1 and other apoptosis-related genes, combined with clinical parameters, can predict response to thiopurines.

Methods:

A retrospective cohort of 156 thiopurine-treated patients with Crohn's disease was genotyped for 11 single-nucleotide polymorphisms (SNPs): 9 SNPs in Rac1, 1 SNP in the Fas ligand −843 T>C, and 1 SNP in the Caspase-9 93 C>T. Clinical data were extracted from the medical charts. Odds ratios (ORs) and 95% confidence intervals (CIs) of the association between demographic, clinical, and genetic variables and thiopurine response rates were calculated.

Results:

The overall response rate to thiopurines was 74% (115/156). The Rac1 SNP rs34932801 heterozygote genotype GC was associated with a lower response rate compared with the wild-type GG genotype (46% versus 76%; OR = 0.26; 95% CI, 0.08–0.91; P = 0.036). Only wild-type homozygotes were found for 5 Rac1 SNPs. None of the other 3 Rac1 SNPs were associated with response to thiopurines. Patients with Montreal B3 behavior pattern responded worse than those with a B1 behavior pattern (59%, versus 80%; OR = 0.37; 95% CI, 0.17–0.83; P = 0.016). Sephardic Jews had a lower response rate to thiopurines compared with Jews of Ashkenazi or mixed ancestry (60% versus 82%; OR = 0.32; 95% CI, 0.15–0.69, P = 0.003).

Conclusions:

Rac1 SNP rs34932801carriage, Montreal B3 disease behavior, and a Sephardic Jewish origin were associated with unfavorable response to thiopurines. Corroboration of these associations in larger cohorts is warranted.

Copyright © 2013 Crohn's & Colitis Foundation of America, Inc.

You currently do not have access to this article.

You may need to:

Note: If your society membership provides for full-access to this article, you may need to login on your society’s web site first.

Login

Search for Similar Articles
You may search for similar articles that contain these same keywords or you may modify the keyword list to augment your search.