SUSCEPTIBILITY TO ULCERATIVE-COLITIS AND CROHNS-DISEASE - INTERACTIONS BETWEEN GLUTATHIONE-S-TRANSFERASE GSTM1 AND GSTT1 GENOTYPES

The polymorphic glutathione S-transferase GSTM1 and GSTT1 loci are attractive candidates for susceptibility to ulcerative colitis and Crohn's disease because their enzymes catalyse the detoxification of products of oxidative stress and tobacco-derived carcinogens. We have tested this hypothesis by comparing genotype frequencies in 245 ulcerative colitis, 112 Crohn's disease patients and 373 controls, Polymerase chain reaction approaches were used to identify the GSTM1 A, GSTM1 B, GSTM1 A/B, GSTM1 null and GSTT1 null and GSTT1 positive genotypes, The ages and smoking characteristics of ulcerative colitis and Crohn's patients were significantly different. Frequencies of GSTM1 genotypes in distal and total ulcerative colitis and controls were not different though frequency of GSTT1 null was significantly greater in the total disease (34.6%) than in the distal disease (17.5%) and control groups (17.7%), The age-corrected odds ratio for GSTT1 null was 2.40 (P = 0.0077). The frequency of GSTT1 null in the Crohn's patients and controls was similar though the frequency of GSTM1 B (7.3%) was significantly reduced compared with controls (15.0%) and patients with distal ulcerative colitis (19.9%). These data indicate that GSTM1 and GSTT1 mediate risk of certain inflammatory pathologies but are not general markers of susceptibility to such diseases, They also contribute to data showing that susceptibility to distal and total ulcerative colitis and Crohn's disease are influenced by different genes.