Influence of polymorphism in the manganese superoxide dismutase locus on disease outcome in rheumatoid arthritis - Evidence for interaction with glutathione S-transferase genes

Objective. To determine whether polymorphism in the manganese superoxide di smutase (MnSOD) gene is associated with susceptibility or disease outcome i n rheumatoid arthritis (RA). Methods. We used a case-control approach with 153 RA patients and 218 contr ol subjects to examine for any associations between MnSOD genotypes and sus ceptibility to RA, We also investigated the influence of genotypes on radio logic outcome, as measured using the Larsen score for radiographs of the ha nds and feet, and on functional outcome, as assessed by the Health Assessme nt Questionnaire. MnSOD typing was carried out using polymerase chain react ion-based methods. Results were analyzed using multiple regression analysis , with adjustment for age, sex, and disease duration. In separate analyses, we corrected for rheumatoid factor (RF) status and/or the presence of the HLA-DRB1 "shared epitope" (SE). We also examined whether radiologic outcome was influenced by interactions between MnSOD and glutathione S-transferase (GST) genes. Results. No association between MnSOD genotype and development of RA was fo und. The MnSOD VV genotype was associated with a significantly higher (P = 0.04) Larsen score (104.4) than MnSOD AA (83.0), while MnSOD AV was associa ted with an intermediate score (91.8). Correction for RF status had no sign ificant effect on the results of the analysis, but significance was lost (P = 0.09) after correction for the presence of the SE, There was evidence of interaction between the GSTT1 and MnSOD genotypes, with the MnSOD VV/GSTT1 -null combination being associated with the highest Larsen score (142.1; P = 0.007 after correction for the SE). Conclusion. Polymorphism in the MnSOD gene is not associated with susceptib ility to RA. Our data suggest that MnSOD VV is associated with more severe radiologic outcome, although this relationship may not be independent of th e effect of the SE. However, interaction between MnSOD and GST genes appear s to influence radiologic outcome independently of the SE.