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Catechol-O-methyltransferase gene haplotypes in Mexican and Spanish patients with fibromyalgia

Gilberto Vargas-Alarcón1, José-Manuel Fragoso1, David Cruz-Robles1, Angélica Vargas1, Alfonso Vargas1, José-Ignacio Lao-Villadóniga2, Ferrán García-Fructuoso3, Manuel Ramos-Kuri4, Fernando Hernández4, Rashidi Springall1, Rafael Bojalil1, Maite Vallejo1 and Manuel Martínez-Lavín1*

Author Affiliations

1 National Institute of Cardiology, Juan Badiano 1, Mexico City 14080, Mexico

2 Dr. Echevarne Laboratory, Provenza 312, Barcelona E08037, Spain

3 CIMA Clinic, Manuel Girona 33, Barcelona E08034, Spain

4 Panamerican University, Donatelo 59, Mexico City 03920, Mexico

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Arthritis Research & Therapy 2007, 9:R110  doi:10.1186/ar2316

See related letter by Martinez and Cassol,, and related response by Eisinger,

Published: 26 October 2007


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.