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Ann Rheum Dis 67:1759-1764 doi:10.1136/ard.2007.083782
  • Basic and translational research

Association between β2 adrenergic receptor polymorphisms and rheumatoid arthritis in conjunction with human leukocyte antigen (HLA)-DRB1 shared epitope

  1. O Malysheva,
  2. M Pierer,
  3. U Wagner,
  4. M Wahle,
  5. U Wagner,
  6. C G Baerwald
  1. Medical Clinic IV, University Hospital, Liebigstraße 22, Leipzig, 04103 Germany
  1. O Malysheva, Medical clinic IV, University Hospital, Liebigstraße 22, 04103 Leipzig Germany; Olga.Malysheva{at}medizin.uni-leipzig.de
  • Accepted 28 January 2008
  • Published Online First 11 February 2008

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.

Footnotes

  • Competing interests: None declared.

  • Funding: This study was supported by grants from Bundesministerium für Bildung und Wissenschaft (BMBF), Kompetenznetzwerk Entzündlich-rheumatische Systemerkrankungen, Teilprojekt Baerwald, no. 01 GI 9955 and the fellowship grants to OM from the European League Against Rheumatism (2004) and the programme “Michail Lomonosov” (2005) with combined support of the German Academic Exchange Service and the Ministry of Science and Education of the Russian Federation.

  • Ethics approval: Ethics approval was obtained.