Glutathione S-transferase M1, T1, and P1 genotypes and rheumatoid arthritis

OBJECTIVE: To determine the effects of genetic polymorphisms of glutathione S-transferase (GST) M1, GSTT1, and GSTP on risk and severity of rheumatoid arthritis (RA) in a Korean population. METHODS: A total of 258 patients with RA and 400 disease-free controls were enrolled. GST genotypes were determined by RFLP-PCR. HLA-DRB 1 typing and further subtyping of all alleles was performed using sequence-specific oligonucleotide probe hybridization after PCR. Severity of RA among cases was assessed by Steinbrocker anatomical stage. Risk was assessed by calculating the age and sex adjusted odds ratio (OR) and 95% confidence intervals (CI). RESULTS: The OR for risk of RA with the GSTM1-null genotype was 1.40 (95% CI 1.02- 1.92, p = 0.04), and 1.86 (95% CI 1.12- 3.09, p = 0.005) among individuals without the shared epitope (SE). Among patients with RA, the OR for risk of severe RA for the GSTM1-null genotype was 2.45 (95% CI 1.04- 5.77, p = 0.02). No association was observed between the GSTT1 or GSTP1 genotypes and either risk or severity of RA. CONCLUSION: These results suggest that the deletion polymorphism of GSTM1 is associated with increased susceptibility for RA, particularly among individuals who are not carriers of the HLA-DRB 1 SE.