RESEARCH - Association between beta-2AR polymorphisms and RA in conjunction with HLA-DRB1 shared epitope

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Published Online First: 11 February 2008. doi:10.1136/ard.2007.083782

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BASIC AND TRANSLATIONAL RESEARCH

Association between ¥â2 adrenergic receptor polymorphisms and

rheumatoid arthritis in conjunction with human leukocyte antigen

(HLA)-DRB1 shared epitope

O Malysheva , M Pierer , U Wagner , M Wahle , U Wagner , C G Baerwald

Medical Clinic IV, University Hospital, Liebigstra©¬e 22, Leipzig, 04103 Germany

Objective: In the present work, the frequency of inherited

polymorphisms of the ¥â2 adrenergic receptor (¥â2AR) 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 ¥â2AR 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 ¥â2AR polymorphisms at

codon 16, contributing (together with the HLA-DR alleles) to the

genetic background of RA.

http://ard.bmj.com/cgi/content/abstract/67/12/1759?etoc

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