Glucocorticoid receptor gene polymorphisms and susceptibility to rheumatoid arthritis

BACKGROUND A defect in hypothalamic-pituitary-adrenal (HPA) axis function has been suggested to contribute to susceptibility to rheumatoid arthritis (RA). OBJECTIVE To investigate polymorphisms of the glucocorticoid receptor (GR) gene and determine any associations with RA. METHODS Three GR polymorphisms that tag 95% of all haplotypes across the GR gene were genotyped. These are an intron B Bcl1 polymorphism, a ttg insertion/deletion within intron F (rs2307674) and the single nucleotide polymorphism (SNP) lying in the 3' untranslated region of exon 9b (rs6198). The dye terminator-based SNaPshot method or size resolution by capillary electrophoresis was performed. The study population comprised 198 UK Caucasian RA cases and 393 ethnically matched controls. RESULTS No significant single point or haplotypic associations were found for GR polymorphisms with RA susceptibility. Furthermore, no evidence for GR polymorphisms with aspects of RA severity was seen. CONCLUSION In this study of the most comprehensive coverage of GR polymorphisms with RA, no significant contributing role for GR polymorphisms with RA was found.