TY - JOUR
T1 - Non-jewish Israeli IBD patients have significantly higher glutathione S-transferase GSTT1-null frequency
AU - Karban, Amir
AU - Krivoy, Norberto
AU - Elkin, Hela
AU - Adler, Lior
AU - Chowers, Yehuda
AU - Eliakim, Rami
AU - Efrati, Edna
N1 - Funding Information:
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).
PY - 2011/7
Y1 - 2011/7
N2 - 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.
AB - 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.
KW - Crohn's disease
KW - Genotype
KW - Glutathione S-transferase
KW - IBD
KW - Ulcerative colitis
UR - http://www.scopus.com/inward/record.url?scp=79959685843&partnerID=8YFLogxK
U2 - 10.1007/s10620-010-1543-4
DO - 10.1007/s10620-010-1543-4
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C2 - 21243434
AN - SCOPUS:79959685843
SN - 0163-2116
VL - 56
SP - 2081
EP - 2087
JO - Digestive Diseases and Sciences
JF - Digestive Diseases and Sciences
IS - 7
ER -