Non-Jewish Israeli IBD patients have significantly higher glutathione S-transferase GSTT1-null frequency

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.