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.
J Rheumatol. 2011 Jun;38(6):1095-103. doi: 10.3899/jrheum.101104. Epub 2011 Mar 16.
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.
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.
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.
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.
通过与无关的健康对照比较，确定纤维肌痛综合征（FM）患者ß（2）-肾上腺素能受体（ß（2）AR）基因多态性（Gly16Arg、Glu27Gln）的基因型频率。我们寻求这些多态性与临床的任何关联，并确定这些多态性是否与 FM 中的生物鸟苷蛋白偶联刺激受体（Gs）功能障碍有关。
研究对象包括 97 例临床特征明确的 FM 患者和 59 例对照。使用聚合酶链反应-限制性片段长度多态性确定ß（2）AR 密码子 16 和 27 处的多态性。使用异丙肾上腺素（ISO）作为肾上腺素能 Gs 配体，测量外周血单核细胞（PBMC）中的细胞内环磷酸腺苷（cAMP）水平，测试 Gs 功能。
FM 中ß（2）AR 基因多态性 Gly16Arg 的频率（43.5%）明显低于对照组（63.2%），表明该基因型可能对 FM 发病风险有一定影响。FM 中唯一的临床关联是睡眠功能障碍。携带ß（2）AR 多态性 Arg16Arg 的 FM 患者 PBMC 的基础 cAMP 水平也明显较低（p < 0.05），ISO 刺激的 cAMP 水平也明显较低（p < 0.05）比携带 Gly16Gly 或 Gly16Arg 的 FM。
这证实了ß（2）AR 多态性与 FM 之间存在关系。这是第一项研究表明，在体外ß（2）AR 刺激后，FM PBMC 中细胞内 cAMP 反应的ß（2）AR 多态性相关差异。这些发现可能解释了 FM 亚组对目前批准用于 FM 治疗的肾上腺素能激动剂药物的反应性差异的部分原因。
