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Logo of bmcmudisBioMed Centralsearchsubmit a manuscriptregisterthis articleBMC Musculoskeletal Disorders
 
BMC Musculoskelet Disord. 2012; 13: 23.
Published online Feb 20, 2012. doi:  10.1186/1471-2474-13-23
PMCID: PMC3310736
A SCN9A gene-encoded dorsal root ganglia sodium channel polymorphism associated with severe fibromyalgia
Gilberto Vargas-Alarcon,#1 Edith Alvarez-Leon,#1 Jose-Manuel Fragoso,#1 Angelica Vargas,#2 Aline Martinez,#2 Maite Vallejo,#3 and Manuel Martinez-Lavincorresponding author2
1Department of Molecular Biology, National Institute of Cardiology Ignacio Chavez, Mexico city, Mexico
2Department of Rheumatology, National Institute of Cardiology Ignacio Chavez, Mexico city, Mexico
3Department of Sociomedical Investigation, National Institute of Cardiology Ignacio Chavez, Mexico city, Mexico
corresponding authorCorresponding author.
#Contributed equally.
Gilberto Vargas-Alarcon: gvargas63/at/yahoo.com; Edith Alvarez-Leon: edalvaleo/at/yahoo.com; Jose-Manuel Fragoso: mfragoso1275/at/yahoo.com.mx; Angelica Vargas: vargasgan/at/yahoo.com; Aline Martinez: alinemtz2/at/yahoo.es; Maite Vallejo: maite_vallejo/at/yahoo.com.mx; Manuel Martinez-Lavin: drmartinezlavin/at/gmail.com
Received May 9, 2011; Accepted February 20, 2012.
Abstract
Background
A consistent line of investigation suggests that autonomic nervous system dysfunction may explain the multi-system features of fibromyalgia (FM); and that FM is a sympathetically maintained neuropathic pain syndrome. Dorsal root ganglia (DRG) are key sympathetic-nociceptive short-circuit sites. Sodium channels located in DRG (particularly Nav1.7) act as molecular gatekeepers for pain detection. Nav1.7 is encoded in gene SCN9A of chromosome 2q24.3 and is predominantly expressed in the DRG pain-sensing neurons and sympathetic ganglia neurons. Several SCN9A sodium channelopathies have been recognized as the cause of rare painful dysautonomic syndromes such as paroxysmal extreme pain disorder and primary erythromelalgia. The aim of this study was to search for an association between fibromyalgia and several SCN9A sodium channels gene polymorphisms.
Methods
We studied 73 Mexican women suffering from FM and 48 age-matched women who considered themselves healthy. All participants filled out the Fibromyalgia Impact Questionnaire (FIQ). Genomic DNA from whole blood containing EDTA was extracted by standard techniques. The following SCN9A single-nucleotide polymorphisms (SNP) were determined by 5' exonuclease TaqMan assays: rs4371369; rs4387806; rs4453709; rs4597545; rs6746030; rs6754031; rs7607967; rs12620053; rs12994338; and rs13017637.
Results
The frequency of the rs6754031 polymorphism was significantly different in both groups (P = 0.036) mostly due to an absence of the GG genotype in controls. Interestingly; patients with this rs6754031 GG genotype had higher FIQ scores (median = 80; percentile 25/75 = 69/88) than patients with the GT genotype (median = 63; percentile 25/75 = 58/73; P = 0.002) and the TT genotype (median = 71; percentile 25/75 = 64/77; P = 0.001).
Conclusion
In this ethnic group; a disabling form of FM is associated to a particular SCN9A sodium channel gene variant. These preliminary results raise the possibility that some patients with severe FM may have a dorsal root ganglia sodium channelopathy.
Keywords: Fibromyalgia, SCN9A, Sodium channels, Sympathetic pain, Dorsal root ganglia, Sympathetic nervous system, Autonomic nervous system, Neuropathic pain, Sodium channelopathy
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