Purpose: The frequency of inherited polymorphisms of the β2-adrenergic receptor (β2AR) gene and the association with rheumatoid arthritis (RA) as well as HLA-DRB1 alleles was examined.
Methods: An allele-specific polymerase chain reaction was used to determine the common variants of the β2AR at position 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 RA patients (89.7 %) compared to 202 controls (66.2%; OR 4.43, 95 % CI 2.81 to 7.02, p=0.00001). Homozygosity for Arg16 was found in 107 RA patients (34.5 %) compared to 14 controls (4.6 %; OR 10.9, CI 5.9 to 20.5, p=0.00001). 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 age at disease onset compared to patients without Arg16 (46.1±2.0 versus 53.1±2.7 respectively, p<0.05). Furthermore, 93.3% patients with homozygosity for Arg16 are positive for anti-CCP antibodies versus 75% patients with homozygosity for Gly16 (p<0.05).
Conclusion: Between RA patients and controls there was a highly significant distortion in the distribution of β2AR polymorphisms at codon 16 contributing together with the HLA-DR alleles to the genetic background of RA.
- German population
- rheumatoid arthritis
- ß2-adrenergic receptor