Large candidate gene association study reveals genetic risk factors and therapeutic targets for fibromyalgia

Abstract

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. Methods Four hundred ninety-six 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 between cases and controls were observed for three genes: GABRB3 (rs4906902, p = 3.65×10−6), TAAR1 (rs8192619, p = 1.11×10−5) and GBP1 (rs7911, p = 1.06×10−4). 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 TAAR1, RGS4, CNR1, and GRIA4 genes. Conclusion 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.

Fibromyalgia Syndrome in Need of Effective Treatments

“…A large candidate gene association study examined over 350 genes in 496 FMS patients and 348 chronic-pain-free controls; three unsuspected genes [gamma-aminobutyric acid receptor subunit-b3 (GABRB3), trace amine receptors (TAAR1) and guanylate binding protein 1 (GBP1)] harbored singlenucleotide polymorphisms that differed in frequency between FMS patients and healthy controls (Smith et al, 2012).…”

Polymorphisms of catechol-O-methyltransferase ( COMT rs4680:G>A ) and μ-opioid receptor ( OPRM1 rs1799971:A >G ) in relation to pain perception in combat athletes

“…There is a suggestion that about half of the variation in individual sensitivity to pain is associated with the influence of genetic factors [17]. More than 350 candidate pain genes have been identified as potentially involved in hereditary differences in pain sensitivity [18]. The contribution of each gene is likely to have only a subtle effect on this multiplicity of mechanisms, making its signal difficult to detect.…”

Dolor miofascial en el territorio craneocervical: una revisión de la patología y su relación con polimorfismos genéticos del sistema GABAérgico

“…Varios polimorfismos genéticos se han descrito de los receptores GABA A (17), algunos han sido asociados a limitaciones motoras como el polimorfismo rs1805057 del gen GABRB1 (GABA A ) encontrándose un haplotipo asociado a una menor limitación en el movimiento en procesos de dolor agudo, sugiriendo que esta subunidad actuaría como un relajante muscular endógeno con una acción GABAérgica inhibitoria mayor que reduciría el espasmo muscular y permitiría mayor movimiento (23). Otro caso es el polimorfismo rs4906902 del gen GABRB3 (GABA A ) que se ha asociado a la presencia de un complejo síndrome caracterizado por dolor musculoesquelético denominado fibromialgia (24).…”