ß2-Adrenergic receptor gene single-nucleotide polymorphisms are associated with rheumatoid arthritis in northern Sweden

Abstract

The β2-adrenergic receptor (β2-AR) belongs to the group of G-protein-coupled receptors and is present on skeletal and cardiac muscle cells and on lymphocytes. The gene encoding β2-AR (ADRB2) displays a moderate degree of heterogeneity in the human population and the distributions of single-nucleotide polymorphisms (SNPs) at amino acid positions 16, 27, and 164 are changed in asthma, obesity, and hypertension and in the autoimmune disease myasthenia gravis. An involvement of the β2-AR has also been suggested in human rheumatoid arthritis (RA) and its animal model. We describe here an increased prevalence of the alleles Arg16 and Gln27 and a lower prevalence of homozygosis for Gly16 and Glu27 in patients with RA. Patients having the genotype combination GlyGly16-GlnGlu27 had higher levels of rheumatoid factor (RF) and a more active disease than other patients. Patients having the genotype Arg16<formula>⁻</formula>Gln27<formula>⁺</formula> had higher levels of RF when compared to those having Arg16<formula>⁺</formula>Gln27<formula>⁺</formula>, and patients who were carriers of Gln27 had a more active disease than non-carriers of Gln27. Our results show an association of β2-AR SNPs with RA in a population from the northern part of Sweden. Our study also confirms the strong linkage disequilibrium of genotypes at amino acid positions 16 and 27.