Biomarkers in fibromyalgia: a review

Figures & data

Table 1 Genetic alteration in FM

Authors	Year	Reference	Findings
Caccamo et al	2013	9	The authors compared the frequency of gene polymorphisms of selected CYP P450 metabolizing enzymes and the frequency of the xenobiotic AHR, in three cohorts and 80 FM patients. They found a significantly higher frequency of CYP and AHR polymorphisms in patients compared with controls
Smith et al	2012	10	The authors studied 350 genes involved in nociception, inflammation, and mood disorders in a large (496) cohort of FM patients and 346 pain-free controls They found significant differences in three genes involved in amine transport: GABRB3, TAARI, and GBPI
Xiao et al	2012	8	The authors evaluated the Val66Met polymorphism (SNP) in the BDNF gene, in 95 FM patients. The frequency of this polymorphism did not differ from healthy controls, but the subgroup with BDNF Val66Val showed higher CRP and BMI
Potvin et al	2010	11	The authors compared 58 FM patients with healthy controls to evaluate thermal pain thresholds and the correlation with the 5-HTTLPR polymorphism. They found higher pain thresholds in the healthy controls compared with those in the FM patients and no correlation with 5-HTTLPR
Cohen et al	2009	12	The authors studied 209 FM patients for the Val/Met polymorphism in the COMT gene. They observed an association between FM and the COMT Val(158)Met polymorphism
Ablin et al	2009	13	The authors studied the frequency of the polymorphism of three candidate genes in 87 FM patients: the substance P receptor (TACRI) 1354 G>C, DAT, and AAT. They didn’t find differences among the FM patients
Tander et al	2008	14	The authors did not find any difference in the COMT (rs4680) and 5-HT2A (rs63l3 and rs63ll) genes in 80 FM patients
Gürsoy et al	2008	15	The authors evaluated the MAO-A and MAO-B polymorphism in l07 FM patients. They suggested the possible relation between the high-activated MAO-A allele 3 in the occurrence of FM

Abbreviations: 5-HT2A, 5-hydroxytryptamine (serotonin) receptor 2A; 5-HTTLPR, serotonin-transporter-linked polymorphic region; AHR, sensor aryl hydrocarbon receptor; BDNF, brain-derived neurotrophic factor; CYP, cytochrome; BMI, body mass index; COMT, catechol-O-methyltransferase; CRP, C-reactive protein; DAT, dopamine transporter; FM, fibromyalgia; GABRB3, gamma-aminobutyric acid (GABA) A receptor, beta 3; GBP1, interferon-induced guanylate-binding protein 1; MAO, monoamine oxidase; Met, methionine; SNP, single nucleotide polymorphism; TAAR1, trace amine-associated receptor 1; TACR1, tachykinin receptor 1; Val, valine.

Table 2 Alteration of oxidative response system and FM

Authors	Year	Reference	Findings
Meeus et al	2013	28	The authors hypothesized that the increase of ROS in FM was due to mitochondria dysfunction
Castro-Marrero et al	2013	29	The authors investigated the possible association between mitochondrial biogenesis and oxidative stress in 23 patients with CFS and in 20 with FM. They found decreased levels of coenzyme Q10 and ATP, together with increased levels of lipid peroxidation. These results suggest a mitochondria involvement in FM
Neyal et al	2013	30	The researchers studied plasma nitrite levels, total antioxidant status, total oxidant status, and oxidative stress index in 33 FM patients and 31 healthy controls. The main result was the higher level of total oxidant status and oxidative stress index in FM patients with respect to controls
Bote et al	2012	31	The authors studied circulating “neuroendocrine-stress” biomarkers (CRH, ACTH, cortisol, NA, eHsp72, serotonin, and IGF-1). Serum cytokines levels and CRP concentrations were also determined. FM patients showed an inflammatory state accompanied by an altered stress response. This was mainly manifested by high circulating levels of IL-8 and high levels of stress molecules
Giacomelli et al	2011	32	By a proteomic approach, we found some altered proteins in saliva of FM patients. In particular, regarding oxidative stress, we found higher levels of calgranulin A and C, which are involved in oxidative stress response
Altindag et al	2007	33	The authors studied paraoxonase and arylesterase levels in 42 FM, and they found a decrease of antioxidative status in FM patients

Abbreviations: ACTH, adrenocorticotropic hormone; ATP, adenosine triphosphate; CFS, chronic fatigue syndrome; CRH, corticotropin-releasing hormone; CRP, C-reactive protein; eHsp, extracellular heat shock protein; FM, fibromyalgia; IGF, insulin-like growth factor; IL, interleukin; NA, noradarenaline; ROS, reactive oxygen species.

Table 3 Cytokines and FM

Bote et al	2013	35	The authors evaluated the effect of moderate physical activity on inflammatory serum components, such as IL-8, chemotaxis activity and O2(−) production by neutrophils, IL-1 β, TNF-α, IL-6, IL-10, and IL-18 release by monocytes, and stress (cortisol, NA, and eHsp72). The authors found that a single session of moderate exercise led to an improvement of the inflammatory status and a decrease in stress molecules
Pernambuco et al	2013	36	The authors evaluated plasma levels of IL-17 in 58 FM patients. They found increased levels of IL-17 and a positive correlation between IL-17 levels and other cytokines (IL-2, IL-4, IL-10, and TNF and IFNγ)
Ross et al	2010	37	The authors evaluated various cytokines and their relationship between GH response and physical exercise. They found higher values of IL-6 and IL-8 in general and higher levels of GH in response to exercise, in FM
lannuccelli et al	2010	38	They found higher levels of IL-IRA, IL-6, IL-10, and TNF-α in FM patients compared with tension-type headache patients and healthy controls
Togo et al	2009	39	They studied the cytokine levels fluctuation over time in eight FM patients compared with the healthy subjects. FM patients showed a trend to increased IL-10 levels during the night compared with controls
Bazzichi et al	2007	40	They studied 80 FM patients compared with 45 healthy subjects, finding higher levels of IL-10, IL-8, and TNF-α in the FM patients compared with the control group

Abbreviations: eHsp, extracellular heat shock protein; FM, fibromyalgia; GH, growth hormone; IFN, interferon; IL, interleukin; NA, noradrenaline; O₂(-), reactive oxigen species; TNF, tumor necrosis factor.