A combination of genetic predisposition and interactions with environmental factors are believed to be responsible for disease phenotype and disease progression in inflammatory bowel diseases. The harmful effect of smoking and other environmental factors is believed to be highly dependent on the activity of detoxification enzymes. The aims of the study were to examine possible associations between the detoxifying glutathione S-transferases (GSTs) family mu, theta and pi gene variants and inflammatory bowel disease, and secondly to examine a potential genotype-genotype interaction between these variants. Genotype-disease phenotype associations and a possible interaction between genotype and cigarette smoking were also assessed.
Three hundred and eighty-eight patients with Crohn's disease (CD), 565 patients with ulcerative colitis (UC) and 796 healthy Danish controls were included in the study. Genomic DNA was used for genotyping of the GST genes using PCR or real-time PCR.
No associations were found between GST genotypes and inflammatory bowel diseases. Neither did a combination of the GST genotypes reveal any associations. No genotype-disease phenotype associations were found. Smoking was positively associated with CD and negatively associated with UC. An interaction between smoking and GSTM1*0 genotype was found for UC, where the GSTM1*0 genotype appear to strengthen the protective effect of smoking on disease susceptibility.
The GST genotypes do not seem to be important in susceptibility of inflammatory bowel disease in the Danish population. Nor did we find convincing evidence of associations between GST genotype and phenotypic features of inflammatory bowel diseases.