Genetic polymorphisms of glutathione S-transferases and disease activity of rheumatoid arthritis

• Published in: Clinical and experimental rheumatology Vol. 27; no. 2; pp. 229 - 236
• Main Authors: BOHANEC GRABAR, P, LOGAR, D, TOMSIC, M, ROZMAN, B, DOLZAN, V
• Format: Journal Article
• Language: English
• Published: Pisa Clinical and Experimental Rheumatology 01.03.2009
• Subjects: Aged; Arthritis, Rheumatoid - genetics; Biological and medical sciences; Diseases of the osteoarticular system; Female; Genotype; Glutathione S-Transferase pi - genetics; Glutathione Transferase - genetics; Humans; Inflammatory joint diseases; Male; Medical sciences; Middle Aged; Polymorphism, Single Nucleotide; Severity of Illness Index; Smoking - adverse effects; Smoking - genetics; Tobacco, tobacco smoking; Toxicology; Immunopathology; Disease activity; Enzyme; Activity index; Transferases; Diseases of the osteoarticular system; Rheumatology; Tobacco smoking; Autoimmune disease; Inflammatory joint disease; Chronic; GST polymorphism; Glutathione transferase; Rheumatoid arthritis; smoking; Genetics; Polymorphism
• ISSN: 0392-856X

Glutathione S-transferases (GST); GST-mu1 (GSTM1), GST-pi1 (GSTP1) and GST-theta1 (GSTT1) have peroxidase activity towards cytotoxic metabolites produced in inflammatory reactions, the main feature of rheumatoid arthritis (RA). Genetic polymorphisms in GSTM1, GSTP1 and GSTT1 modify the enzyme conjugation capacity and may be associated with the activity of RA. A genotyping approach was used to analyze GSTM1-0, GSTT1-0 and GSTP1 Ile105Val and Ala114Val polymorphisms in 213 RA patients. Disease activity was assessed by the disease activity score of 28 joint counts (DAS28) twice for each patient and mean DAS28 values were calculated. The patients with GSTT1-0 genotype had a higher risk for developing high activity RA than the patients with GSTT1 genes present (p=0.028, OR=2.761, 95% CI=1.114-6.843). An interaction between the GSTT1 polymorphism and smoking was observed. In the group of smokers, the carriers of a homozygous deletion GSTT1 had an 8.5-fold higher risk for developing high disease activity than the patients with the GSTT1-1 genotype (p=0.004, OR=8.640, 95% CI=1.995-37.426). GSTM1 and GSTP1 polymorphisms were not associated with the disease activity. Our results suggest that the presence of the GSTT1-0 genotype contributed to higher disease activity in RA patients. The risk for developing highly active RA was the highest in smokers with the GSTT1-0 genotype.