Association between β2 adrenergic receptor polymorphisms and rheumatoid arthritis in conjunction with human leukocyte antigen (HLA)-DRB1 shared epitope. Issue 12 (11th February 2008)

• Record Type: Journal Article
• Authors: Malysheva, O; Pierer, M; Wagner, U; Wahle, M; Wagner, U; Baerwald, C G
• Is Part Of: Annals of the rheumatic diseases. Volume 67:Issue 12(2008)
• Page Start: 1759
• Page End: 1764
• Publication Date: 2008-02-11
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/ard.2007.083782
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Objective: In the present work, the frequency of inherited polymorphisms of the β2 adrenergic receptor (β2AR) gene and their association with rheumatoid arthritis (RA) as well as human leukocyte antigen (HLA)-DRB1 alleles was examined. Methods: An allele-specific polymerase chain reaction was used to determine the common variants of the β2AR at positions 16, 27 and 164 in patients with RA (n = 310) and ethnically matched healthy controls (n = 305) from Germany. HLA-DRB1 genotyping was performed by oligonucleotide hybridisation of enzymatically amplified DNA allowing low-resolution HLA-DRB1 genotyping comprising specificities DRB1*01 to DRB1*17. Results: Arginine (Arg) at codon 16 was present in 278 patients with RA (89.7%) compared to 202 controls (66.2%; odds ratio (OR) 4.43, 95% CI 2.81 to 7.02, p<0.001). Homozygosity for Arg16 was found in 107 patients with RA (34.5%) compared to 14 controls (4.6%; OR 10.9, CI 5.9 to 20.5, p<0.001). Stratifying patients for their HLA-DR status revealed that homozygosity for Arg16 exhibited the greatest risk for RA in combination with HLA-DRB1*04 (OR 17.1, 95% CI 1.71 to 414.4, p = 0.004). Interestingly, patients with the Arg16 allele have a younger mean (SD) age at disease onset compared to patients without Arg16 (46.1 (2.0) vs 53.1 (2.7) respectively, p<0.05). Furthermore, 93.3% patients with homozygosity for Arg16 were positive for anti-cyclic citrullinated peptide (CCP) antibodies vs 75% patients with homozygosity for Gly16 (p<0.05). Conclusion: There was a highly significant distortion between patients with RA and controls in the distribution of β2AR polymorphisms at codon 16, contributing (together with the HLA-DR alleles) to the genetic background of RA.