Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement
The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.
Genetic Polymorphisms of the Beta 2-Adrenergic Receptor Relate to Gs Protein Dysfunction in Fibromyalgia Syndrome
Xiao, Yangming, Jon Russell, I., Haynes, Wanda L., Michalek, Joel E.
The beta 2-adrenergic receptor (b2AR) is a G protein-coupled receptor (GPCR) that mediates the actions of catecholamines in multiple tissues. We previously documented a GPCR stimulatory (Gs) dysfunction in patients with fibromyalgia syndrome (FMS). The aims of the present study were to determine the frequencies of b2AR gene polymorphisms in FMS compared with healthy normal controls (HNC) and to determine whether polymorphisms in the b2AR gene might contribute to the Gs dysfunction in FMS.
The study was conducted with ethics committee approval and study subjects signed informed consent to participate. Morning blood samples were obtained from primary FMS (1990 ACR criteria) and demographically-matched HNC in what was intended to be a ratio of 2:1. Peripheral blood mononuclear cells (PBMC) were isolated by density gradient centrifugation. The Gs functions of PBMC were tested using isoproterenol (ISO) as the adrenergic Gs ligand and measuring intracellular cAMP levels (second message) by enzyme linked immunosorbent assay (ELISA). The b2AR genotypes at amino acid position 16 and 27 were determined for each subject using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Differences between the genotype frequencies of FMS and HNC were evaluated using a chi-square test.
Study subjects included 97 FMS patients and 59 HNC. The frequency of the b2AR gene polymorphism Arg16Gly (45.1%) in FMS was significantly lower (p = 0.035) than in HNC (62.7%). Conversely, the Gly16Gly genotype in FMS (37.1%) was marginally more frequent than in HNC (25.4%, p = 0.06). The frequencies of other tested b2AR genotypes, such as Arg16Arg, Gln27Gln, Glu27Glu, and Gln27Glu did not differ between FMS and HNC. FMS patients carrying the b2AR polymorphism Arg16Arg exhibited significantly lower PBMC basal cAMP levels (p<0.025) and lower ISO-stimulated cAMP levels (p<0.025) than FMS carrying Gly16Gly or Arg16Gly.
These data show that in vitro testing of GPCR function of PBMC can be fruitful in FMS. Several associations were found between FMS and b2AR genetic polymorphisms at codon 16. Indeed, this is the first study to demonstrate b2AR polymorphism-related differences in intracellular cAMP levels within FMS PBMC before and after beta adrenergic stimulation. These findings imply that b2AR polymorphism in FMS may influence responses to a variety of beta adrenergic ligands. This concept may help to explain some of the differences in responsiveness of FMS subgroups to the adrenergic agonist medications currently approved for FMS treatment. Finally, one could speculate that these findings may directly relate to the adrenergic autonomic nervous system dysfunction documented in FMS.
To cite this abstract, please use the following information:
Xiao, Yangming, Jon Russell, I., Haynes, Wanda L., Michalek, Joel E.; Genetic Polymorphisms of the Beta 2-Adrenergic Receptor Relate to Gs Protein Dysfunction in Fibromyalgia Syndrome [abstract]. Arthritis Rheum 2009;60 Suppl 10 :569