A SCN9A gene-encoded dorsal root ganglia sodium channel polymorphism associated with severe fibromyalgia

BMC Musculoskeletal Disorders

Manuel Martinez-Lavin¹  Maite Vallejo³  Aline Martinez¹  Angelica Vargas¹  Jose-Manuel Fragoso²  Edith Alvarez-Leon²  Gilberto Vargas-Alarcon² 

[1] Department of Rheumatology, National Institute of Cardiology Ignacio Chavez, Mexico city, Mexico;Department of Molecular Biology, National Institute of Cardiology Ignacio Chavez, Mexico city, Mexico;Department of Sociomedical Investigation, National Institute of Cardiology Ignacio Chavez, Mexico city, Mexico

关键词: Sodium channelopathy;    Neuropathic pain;    Autonomic nervous system;    Sympathetic nervous system;    Dorsal root ganglia;    Sympathetic pain;    Sodium channels;    SCN9A;    Fibromyalgia;   

Others  :  1150557
DOI  :  10.1186/1471-2474-13-23

 received in 2011-05-09, accepted in 2012-02-20,  发布年份 2012

【 摘 要 】

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.

【 授权许可】

   
2012 Vargas-Alarcon et al; licensee BioMed Central Ltd.

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