肾上腺素能受体基因多态性与不同纤维肌痛综合征领域的关联。

Association of adrenergic receptor gene polymorphisms with different fibromyalgia syndrome domains.

作者信息

Vargas-Alarcón Gilberto, Fragoso José-Manuel, Cruz-Robles David, Vargas Angélica, Martinez Aline, Lao-Villadóniga José-Ignacio, García-Fructuoso Ferrán, Vallejo Maite, Martínez-Lavín Manuel

机构信息

National Institute of Cardiology Ignacio Chávez, Tlalpan, Mexico City, Mexico.

出版信息

Arthritis Rheum. 2009 Jul;60(7):2169-73. doi: 10.1002/art.24655.

DOI:10.1002/art.24655

PMID:19565482

Abstract

OBJECTIVE

Fibromyalgia (FM) patients have signs of relentless sympathetic hyperactivity associated with hyporeactivity to stress. Adrenergic receptors (ARs) are parts of the sympathetic nervous system that are fundamental for maintenance of homeostasis. We undertook this study to correlate alpha-AR and beta-AR gene polymorphisms with the presence of FM and with different domains of the FM syndrome as measured by the Fibromyalgia Impact Questionnaire (FIQ).

METHODS

We studied 78 Mexican FM patients and 48 age-matched controls as well as 78 Spanish FM patients and 71 controls. All subjects studied were women. Single-nucleotide polymorphisms (SNPs) of alpha(1A)-AR (rs574584, rs1383914, rs1048101, and rs573542), beta(2)-AR (rs1042713 and rs1042714), and beta(3)-AR (rs4994) were analyzed by 5' exonuclease TaqMan polymerase chain reaction. Polymorphic haplotypes were constructed after linkage disequilibrium analysis.

RESULTS

The beta(2)-AR AC haplotype was a risk factor for the presence of FM. This haplotype had an increased frequency in Mexican patients compared with Mexican controls (42.1% versus 30.5%; P = 0.04). Similarly, 50.4% of Spanish patients had this haplotype compared with 40.0% of Spanish controls (P = 0.05). In Spanish patients, the alpha(1A)-AR SNP rs1383914 was associated with the presence of FM (P = 0.01), and the alpha(1A)-AR SNP rs1048101 was linked with FIQ disability (P = 0.02). Mexican patients with the rs574584 GG genotype presented the highest FIQ score compared with Mexican patients with other genotypes (P = 0.01), and in Mexicans SNP rs574584 was associated with FIQ morning stiffness (P = 0.04) and with FIQ tiredness upon awakening (P = 0.02).

CONCLUSION

AR gene polymorphisms are related to the risk of developing FM and are also linked to different domains of the FM syndrome.

摘要

目的

纤维肌痛（FM）患者存在持续的交感神经过度活跃迹象，并伴有对应激反应低下。肾上腺素能受体（ARs）是交感神经系统的一部分，对维持体内平衡至关重要。我们开展这项研究，旨在将α-AR和β-AR基因多态性与FM的存在以及通过纤维肌痛影响问卷（FIQ）测量的FM综合征的不同领域相关联。

方法

我们研究了78名墨西哥FM患者和48名年龄匹配的对照，以及78名西班牙FM患者和71名对照。所有研究对象均为女性。通过5'外切酶TaqMan聚合酶链反应分析α(1A)-AR（rs574584、rs1383914、rs1048101和rs573542）、β(2)-AR（rs1042713和rs1042714）和β(3)-AR（rs4994）的单核苷酸多态性（SNPs）。在连锁不平衡分析后构建多态性单倍型。

结果

β(2)-AR AC单倍型是FM存在的一个危险因素。与墨西哥对照相比，该单倍型在墨西哥患者中的频率增加（42.1%对30.5%；P = 0.04）。同样，50.4%的西班牙患者有此单倍型，而西班牙对照为40.0%（P = 0.05）。在西班牙患者中，α(1A)-AR SNP rs1383914与FM的存在相关（P = 0.01），α(1A)-AR SNP rs1048101与FIQ残疾相关（P = 0.02）。与具有其他基因型的墨西哥患者相比，具有rs574584 GG基因型的墨西哥患者FIQ得分最高（P = 0.01），在墨西哥人中，SNP rs574584与FIQ晨僵相关（P = 0.04）以及与觉醒时的FIQ疲劳相关（P = 0.02）。