Glutathione S-Transferase Gene with Susceptibility to Juvenile Idiopathic Arthritis

Abstract

JIA is one of the most common rheumatic disease of children and a leading cause of disability with major individual and health service costs. It is characterized mostly by polyarticular inflammation, increased cytokine production and pannus development, which subsequently lead to the erosion of the cartilage and underlying bone. It begins before the age of 16 years. ROS are involved in JIA pathology, since they are generated by neutrophils, monocytes and macrophages in synovial fluid of inflamed joints and cause DNA and lipid oxidation leading to cartilage and bone destruction. The defense mechanism against ROS is complex and involves several enzymes including GSTs. GSTs enzymes constitute a family of cytosolic isoenzymes that are involved in the detoxification of electrophilic xenobiotics. They represent an important group of enzymes which detoxify both endogenous compounds and foreign chemicals such as pharmaceuticals and environmental pollutant. Numerous polymorphisms exist in the human GSTs genes, GSTM1 and GSTT1 genes are affected by deletion polymorphisms which result indeficient conjugating activity with decrease of their functions which may be associated with increased sensitivity to toxic. Several studies have demonstrated that multiple allelic polymorphisms at loci encoding detoxifying enzymes are the basis of inter- individual variation in detoxification metabolism. Differences in genetic susceptibility to diseases can be partly attributed to inter-individual variation in metabolic activity. This study was conducted on 80 children; selected from pediatric allergy and immunology clinic Ain Shams University. Group A, 40 patients (13 male and 27 female) in ratio of 1: 2 for total cases with JIA and group B, 40 apparently healthy children (18 male and 22 female) in a ratio of 0.8: 1.2, with matched age and sex served as controls. The mean age of studied cases was 9.25±4.55 years and the mean age of controls was 8.46±3.77. Molecular identification of GSTM1and GSTT1 polymorphisms was carried out using allelic discrimination by PCR. 47.5% of the studies patients were Polyarticular type, while 30% was systemic and 22.5% was pauciarticular. All patients received NSAIDs, 65% received systemic corticosteroids, while 42.5% received methotrexate. The result of this study revealed that: • The null frequency of GSTM1 genotypes was higher in JIA patients than controls.