Ernst Anja, Andersen Vibeke, Østergaard Mette, Jacobsen Bent A, Dagiliene Enrika, Pedersen Inge S, Drewes Asbjørn M, Okkels Henrik, Krarup Henrik B
Department of Clinical Biochemistry, Section of Molecular Diagnostics, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark.
Scand J Gastroenterol. 2010 Sep;45(9):1068-75. doi: 10.3109/00365521.2010.490594.
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 GSTM10 genotype was found for UC, where the GSTM10 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.
遗传易感性与环境因素相互作用被认为是导致炎症性肠病疾病表型和疾病进展的原因。吸烟和其他环境因素的有害影响被认为高度依赖于解毒酶的活性。本研究的目的一是检测解毒谷胱甘肽S-转移酶（GSTs）家族中的μ、θ和π基因变异与炎症性肠病之间可能存在的关联，二是检测这些变异之间潜在的基因型-基因型相互作用。还评估了基因型与疾病表型的关联以及基因型与吸烟之间可能存在的相互作用。
本研究纳入了388例克罗恩病（CD）患者、565例溃疡性结肠炎（UC）患者和796名丹麦健康对照者。使用PCR或实时PCR对基因组DNA进行GST基因分型。
未发现GST基因型与炎症性肠病之间存在关联。GST基因型的组合也未显示出任何关联。未发现基因型与疾病表型之间的关联。吸烟与CD呈正相关，与UC呈负相关。在UC中发现吸烟与GSTM10基因型之间存在相互作用，其中GSTM10基因型似乎增强了吸烟对疾病易感性的保护作用。
在丹麦人群中，GST基因型似乎对炎症性肠病的易感性并不重要。我们也没有找到令人信服的证据证明GST基因型与炎症性肠病的表型特征之间存在关联。
