Inflammatory Bowel Diseases

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*,†

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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.

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

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