Association between beta2 adrenergic receptor polymorphisms and rheumatoid arthritis in conjunction with human leukocyte antigen (HLA)-DRB1 shared epitope.
OBJECTIVE
In the present work, the frequency of inherited polymorphisms of the beta2 adrenergic receptor (beta2AR) 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 beta2AR 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).


CONCLUSIONS
There was a highly significant distortion between patients with RA and controls in the distribution of beta2AR polymorphisms at codon 16, contributing (together with the HLA-DR alleles) to the genetic background of RA.
Malysheva
O
O
Medical Clinic IV, University Hospital, Liebigstrasse 22, 04103 Leipzig Germany. Olga.Malysheva@medizin.uni-leipzig.de
Pierer
M
M
Wagner
U
U
Wahle
M
M
Wagner
U
U
Baerwald
C G
CG
D000328:Adult; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D012720:Severity of Illness Index
D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D018343:Receptors, Adrenergic, beta-2