Genetic Polymorphisms of the ß2-Adrenergic Receptor Relate to Guanosine Protein-coupled Stimulator Receptor Dysfunction in Fibromyalgia Syndrome

Abstract

Objective.To determine the genotype frequencies of ß2-adrenergic receptor (ß2AR) gene polymorphisms (Gly16Arg, Glu27Gln) in patients with fibromyalgia syndrome (FM) by comparison with unrelated healthy controls. We sought any clinical association with these polymorphisms and determined whether the polymorphisms would associate with a biologic guanosine protein-coupled stimulator receptor (Gs) dysfunction in FM.Methods.Study subjects included 97 clinically characterized patients with FM and 59 controls. The ß2AR polymorphisms at codons 16 and 27 were determined using polymerase chain reaction-restriction fragment length polymorphism. The Gs functions of peripheral blood mononuclear cells (PBMC) were tested using isoproterenol (ISO) as the adrenergic Gs ligand and measuring intracellular cyclic adenosine monophosphate (cAMP) levels.Results.The frequency of the ß2AR gene polymorphism Gly16Arg in FM (43.5%) was significantly lower than in controls (63.2%), suggesting that this genotype might have some effect on the risk of developing FM. The only clinical association in FM was with sleep dysfunction. Patients with FM who carried the ß2AR polymorphism Arg16Arg also exhibited significantly lower PBMC basal cAMP levels (p < 0.05) and lower ISO-stimulated cAMP levels (p < 0.05) than FM carrying Gly16Gly or Gly16Arg.Conclusion.This confirms a relationship between ß2AR polymorphism and FM. It is the first study to demonstrate ß2AR polymorphism-related differences in intracellular cAMP responses of FM PBMC after ß2AR stimulationin vitro. These findings may explain some of the differences in responsiveness of FM subgroups to the adrenergic agonist medications currently approved for FM treatment.