Vargas-Alarcón Gilberto, Fragoso José-Manuel, Cruz-Robles David, Vargas Angélica, Vargas Alfonso, Lao-Villadóniga José-Ignacio, García-Fructuoso Ferrán, Ramos-Kuri Manuel, Hernández Fernando, Springall Rashidi, Bojalil Rafael, Vallejo Maite, Martínez-Lavín Manuel
National Institute of Cardiology, Juan Badiano 1, Mexico City 14080, Mexico.
Arthritis Res Ther. 2007;9(5):R110. doi: 10.1186/ar2316.
Autonomic dysfunction is frequent in patients with fibromyalgia (FM). Heart rate variability analyses have demonstrated signs of ongoing sympathetic hyperactivity. Catecholamines are sympathetic neurotransmitters. Catechol-O-methyltransferase (COMT), an enzyme, is the major catecholamine-clearing pathway. There are several single-nucleotide polymorphisms (SNPs) in the COMT gene associated with the different catecholamine-clearing abilities of the COMT enzyme. These SNPs are in linkage disequilibrium and segregate as 'haplotypes'. Healthy females with a particular COMT gene haplotype (ACCG) producing a defective enzyme are more sensitive to painful stimuli. The objective of our study was to define whether women with FM, from two different countries (Mexico and Spain), have the COMT gene haplotypes that have been previously associated with greater sensitivity to pain. All the individuals in the study were female. Fifty-seven Mexican patients and 78 Spanish patients were compared with their respective healthy control groups. All participants filled out the Fibromyalgia Impact Questionnaire (FIQ). Six COMT SNPs (rs2097903, rs6269, rs4633, rs4818, rs4680, and rs165599) were genotyped from peripheral blood DNA. In Spanish patients, there was a significant association between three SNPs (rs6269, rs4818, and rs4680) and the presence of FM when compared with healthy controls. Moreover, in Spanish patients with the 'high pain sensitivity' haplotype (ACCG), the disease, as assessed by the FIQ, was more severe. By contrast, Mexican patients displayed only a weak association between rs6269 and rs165599, and some FIQ subscales. In our group of Spanish patients, there was an association between FM and the COMT haplotype previously associated with high pain sensitivity. This association was not observed in Mexican patients. Studies with a larger sample size are needed in order to verify or amend these preliminary results.
自主神经功能障碍在纤维肌痛(FM)患者中很常见。心率变异性分析已显示出持续交感神经过度活跃的迹象。儿茶酚胺是交感神经递质。儿茶酚-O-甲基转移酶(COMT)作为一种酶,是主要的儿茶酚胺清除途径。COMT基因中有几种单核苷酸多态性(SNP)与COMT酶不同的儿茶酚胺清除能力相关。这些SNP处于连锁不平衡状态,并作为“单倍型”分离。具有产生缺陷酶的特定COMT基因单倍型(ACCG)的健康女性对疼痛刺激更敏感。我们研究的目的是确定来自两个不同国家(墨西哥和西班牙)的FM女性是否具有先前与更高疼痛敏感性相关的COMT基因单倍型。研究中的所有个体均为女性。将57名墨西哥患者和78名西班牙患者与其各自的健康对照组进行比较。所有参与者都填写了纤维肌痛影响问卷(FIQ)。从外周血DNA中对六个COMT SNP(rs2097903、rs6269、rs4633、rs4818、rs4680和rs165599)进行基因分型。在西班牙患者中,与健康对照组相比,三个SNP(rs6269、rs4818和rs4680)与FM的存在之间存在显著关联。此外,在具有“高疼痛敏感性”单倍型(ACCG)的西班牙患者中,通过FIQ评估的疾病更为严重。相比之下,墨西哥患者仅显示rs6269与rs165599以及一些FIQ子量表之间存在弱关联。在我们的西班牙患者组中,FM与先前与高疼痛敏感性相关的COMT单倍型之间存在关联。在墨西哥患者中未观察到这种关联。需要进行更大样本量的研究以验证或修正这些初步结果。