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.