title: Genetic polymorphisms of the beta2-adrenergic receptor relate to guanosine protein-coupled stimulator receptor dysfunction in fibromyalgia syndrome.
abstract: OBJECTIVE
  To determine the genotype frequencies of ß(2)-adrenergic receptor (ß(2)AR) 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 ß(2)AR 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 ß(2)AR 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 ß(2)AR 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.
  
  
  CONCLUSIONS
  This confirms a relationship between ß(2)AR polymorphism and FM. It is the first study to demonstrate ß(2)AR polymorphism-related differences in intracellular cAMP responses of FM PBMC after ß(2)AR stimulation in vitro. These findings may explain some of the differences in responsiveness of FM subgroups to the adrenergic agonist medications currently approved for FM treatment.
authors.affiliation: Division of Clinical Immunology, Department of Medicine, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA. yangming.xiao@utsa.edu
authors.forename: Yangming
authors.initials: Y
authors.lastname: Xiao
authors.forename: Weijing
authors.initials: W
authors.lastname: He
authors.forename: I Jon
authors.initials: IJ
authors.lastname: Russell
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003062:Codon; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D005356:Fibromyalgia / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology*; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000502:physiology*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*
chemical_list: D003062:Codon; D018343:Receptors, Adrenergic, beta-2; D000242:Cyclic AMP; D019205:GTP-Binding Protein alpha Subunits, Gs