Large candidate gene association study reveals genetic risk factors and therapeutic targets for fibromyalgia
– Source: Arthritis & Rheumatism, Sep 8, 2011
By SB Smith, et al.
[Note: an allele is one of two or more possible forms of a gene located at a specific position on a specific chromomosome. Different alleles result in variations of a trait.]
Objective: Fibromyalgia (FM) represents a complex disorder characterized by widespread pain and tenderness and frequently accompanied by additional somatic and cognitive/affective symptoms.
Genetic risk factors are known to contribute to the etiology of the syndrome, but few specific genetic variants have been identified to date and still require replication.
In this study, a large scale candidate gene approach was used to examine over 350 genes for association with FM.
• 496 FM patients were included in the study as cases
• With a total of 348 chronic pain-free controls.
Genotyping was performed using a dedicated gene array chip, the Pain Research Panel, which assays variants characterizing over 350 genes known to be involved in biological pathways relevant to nociception, inflammation, and mood. Association testing was performed using logistic regression.
Results: Significant differences in allele frequencies [alleles are alternative forms of a gene located at a specific position on a specific chromomosome] between cases and controls were observed for three genes:
• GABRB3 (rs4906902, p = 3.65x10(-6) ),
• TAAR1 (rs8192619, p = 1.11x10(-5) )
• And GBP1 (rs7911, p = 1.06x10(-4) ).
These three genes, and seven other genes with suggestive evidence for association, were examined in a second, independent cohort of FM patients and controls genotyped using the Perlegen 600K platform.
Evidence of association in the replication cohort was observed for:
• And GRIA4 genes.
• Variation in these genes may serve as a basis for development of new diagnostic approaches,
• And these genes' products may contribute to the pathophysiology of FM and represent potential targets for therapeutic action.
Source: Arthritis & Rheumatism, Sep 8, 2011. PMID:21905019, by Smith SB, Maixner DW, Fillingim RB, Slade G, Gracely RH, Ambrose K, Zaykin DV, Hyde C, John S, Tan K, Maixner W, Diatchenko L. Algynomics, Inc., Chapel Hill, North Carolina; Center for Neurosensory Disorders, University of North Carolina, Chapel Hill, USA.