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


OBJECTIVE
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.
Internal Medicine C, Rambam Health Care Campus, P.O. Box 9602, Haifa, 31096, Israel. a_karban@rambam.health.gov.il
Amir
A
Karban
Norberto
N
Krivoy
Hela
H
Elkin
Lior
L
Adler
Yehuda
Y
Chowers
Rami
R
Eliakim
Edna
E
Efrati
D000293:Adolescent; D000328:Adult; D018912:Arabs / Q000235:genetics; D002648:Child; D015331:Cohort Studies; D020022:Genetic Predisposition to Disease; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000201:enzymology / Q000453:epidemiology* / Q000235:genetics*; D007557:Israel / Q000453:epidemiology; D007585:Jews / Q000235:genetics; D008297:Male; D053473:Nod2 Signaling Adaptor Protein; D011110:Polymorphism, Genetic; D017384:Sequence Deletion; D012907:Smoking / Q000453:epidemiology; D055815:Young Adult
D005982:Glutathione Transferase; D053473:Nod2 Signaling Adaptor Protein; C429018:NOD2 protein, human; C413545:glutathione S-transferase T1
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