OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
OBJECTIVES: 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. METHODS: A genotyping approach was used to analyze GSTM1-0, GSTT1-0 and GSTP1 Ile105Val and Ala114Val polymorphisms in 213 RApatients. Disease activity was assessed by the disease activity score of 28 joint counts (DAS28) twice for each patient and mean DAS28 values were calculated. RESULTS: 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. CONCLUSION: Our results suggest that the presence of the GSTT1-0 genotype contributed to higher disease activity in RApatients. The risk for developing highly active RA was the highest in smokers with the GSTT1-0 genotype.
Authors: Brendan T Keenan; Lori B Chibnik; Jing Cui; Bo Ding; Leonid Padyukov; Henrik Kallberg; Camilla Bengtsson; Lars Klareskog; Lars Alfredsson; Elizabeth W Karlson Journal: Arthritis Rheum Date: 2010-11
Authors: Yun Liu; Martin J Aryee; Leonid Padyukov; M Daniele Fallin; Espen Hesselberg; Arni Runarsson; Lovisa Reinius; Nathalie Acevedo; Margaret Taub; Marcus Ronninger; Klementy Shchetynsky; Annika Scheynius; Juha Kere; Lars Alfredsson; Lars Klareskog; Tomas J Ekström; Andrew P Feinberg Journal: Nat Biotechnol Date: 2013-01-20 Impact factor: 54.908