polymorphisms in the glucocorticoid receptor gene that modulate glucocorticoid sensitivity are associated with rheumatoid arthritis糖皮质激素受体基因多态性在调节糖皮质激素敏感性与类风湿性关节炎有关.pdf

van Oosten et al. Arthritis Research Therapy 2010, 12:R159 /content/12/4/R159 RESEARCH ARTICLE Open Access Polymorphisms in the glucocorticoid receptor gene that modulate glucocorticoid sensitivity are associated with rheumatoid arthritis 1 2 1 1 3 Manon JM van Oosten , Radboud JEM Dolhain , Jan W Koper , Elisabeth FC van Rossum , Marieke Emonts , Khik H Han4 5 2 1 1* , Jacques MGW Wouters , Johanne MW Hazes , Steven WJ Lamberts , Richard A Feelders Abstract Introduction: The glucocorticoid receptor (GR) plays an important regulatory role in the immune system. Four polymorphisms in the GR gene are associated with differences in glucocorticoid (GC) sensitivity; the minor alleles of the polymorphisms N363 S and BclI are associated with relative hypersensitivity to GCs, while those of the polymorphisms ER22/23EK and 9b are associated with relative GC resistance. Because differences in GC sensitivity may influence immune effector functions, we examined whether these polymorphisms are associated with the susceptibility to develop Rheumatoid Arthritis (RA) and RA disease severity. Methods: The presence of GR polymorphisms was assessed in healthy controls (n = 5033), and in RA patients (n = 368). A second control group (n = 532) was used for confirmation of results. In RA patients, the relationship between GR polymorphisms and disease severity was examined. Results: Carriers of the N363 S and BclI minor alleles had a lower risk of developing RA: odds ratio (OR) = 0.55 (95% confidence interval (CI) 0.32-0.96, P = 0.032) and OR = 0.73 (95% CI 0.58-0.91, P = 0.006), respectively. In c