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Non-Jewish Israeli IBD Patients Have Significantly Higher Glutathione S-Transferase GSTT1-Null Frequency

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Abstract

Background

The involvement of oxidant/antioxidant imbalance in the development of inflammatory bowel disease (IBD) is well documented. Two members of the glutathione S-transferase (GST) family of enzymes, GSTM1 and GSTT1, known to take part in cellular protection against electrophiles, demonstrate common deletion variants (termed null) associated with impaired enzyme function.

Aim

To evaluate the effect of GSTM1/GSTT1 genotype on IBD susceptibility in a Israeli cohort and to study the correlation between GSTM1/GSTT1 genotype, smoking status, and a variety of clinical characteristics of IBD.

Methods

A cohort of 606 Israeli IBD patients (453 with Crohn’s disease [CD] and 153 with ulcerative colitis [UC]) and 528 ethnically matched healthy controls were genotyped for the null variants of GSTM1 and GSTT1. In patients, phenotype–genotype correlations were examined.

Results

Ethnic stratification of healthy controls revealed a higher frequency of GSTT1-null in Jewish and Arab Moslem individuals compared to Druze individuals (P < 0.0005), but no difference in GSTM1-null was found. Comparing IBD patients (both CD and UC) to healthy controls revealed a pattern of lower GSTM1-null and higher GSTT1-null frequencies, which reached significance in Arab Moslem patients. No association was found between NOD2/CARD15 mutation carriage and GSTM1/GSTT1 genotype. No statistically significant association was found between GSTT1-null or GSTM1-null, smoking status, and other phenotypes of CD/UC.

Conclusions

GSTT1-null appears to be associated with IBD, while GSTM1-null appears to be conversely associated with IBD. No association was found between GSTT1-null or GSTM1-null and specific IBD phenotypes.

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Acknowledgments

This study was partially supported by the Newell Foundation Research Fund on the Genetic Studies of Inflammatory Bowel Diseases in Israel (Newell Foundation-10707).

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Authors and Affiliations

  1. Internal Medicine C, Rambam Health Care Campus, P.O. Box 9602, Haifa, 31096, Israel

    Amir Karban

  2. Clinical Pharmacology Institute, Rambam Health Care Campus, Haifa, Israel

    Norberto Krivoy

  3. Center for Translational Genetics, B. Rappaport Institute for Research in the Medical Sciences, Faculty of Medicine, Technion—Israel Institute of Technology and Rambam Health Care Campus, Haifa, Israel

    Norberto Krivoy, Hela Elkin, Lior Adler & Edna Efrati

  4. Department of Gastroenterology, Rambam Health Care Campus, Haifa, Israel

    Amir Karban, Yehuda Chowers & Rami Eliakim

  5. Faculty of Medicine, Technion—Israel Institute of Technology, Haifa, Israel

    Amir Karban, Norberto Krivoy, Yehuda Chowers & Rami Eliakim

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  1. Amir Karban
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  2. Norberto Krivoy
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  3. Hela Elkin
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Correspondence to Amir Karban.

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Karban, A., Krivoy, N., Elkin, H. et al. Non-Jewish Israeli IBD Patients Have Significantly Higher Glutathione S-Transferase GSTT1-Null Frequency. Dig Dis Sci 56, 2081–2087 (2011). https://doi.org/10.1007/s10620-010-1543-4

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  • DOI: https://doi.org/10.1007/s10620-010-1543-4

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