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. 2021 Apr 28;10(9):1902.
doi: 10.3390/jcm10091902.

Fatigue in Women with Fibromyalgia: A Gene-Physical Activity Interaction Study

Fernando Estévez-López  1 , Diego F Salazar-Tortosa  2 , Daniel Camiletti-Moirón  3 , Blanca Gavilán-Carrera  3 , Virginia A Aparicio  4   5 , Pedro Acosta-Manzano  6 , Víctor Segura-Jiménez  3 , Inmaculada C Álvarez-Gallardo  3 , Ana Carbonell-Baeza  3 , Diego Munguía-Izquierdo  7 , Rinie Geenen  8 , Eliana Lacerda  9 , Manuel Delgado-Fernández  6 , Luis J Martínez-González  10 , Jonatan R Ruiz  11 , María J Álvarez-Cubero  12
Affiliations

Fatigue in Women with Fibromyalgia: A Gene-Physical Activity Interaction Study

Fernando Estévez-López et al. J Clin Med. .

Abstract

Fatigue is a cardinal symptom in fibromyalgia. Fatigue is assumed to be the result of genetic susceptibility and environmental factors. We aimed at examining the role of genetic susceptibility for fatigue in southern Spanish women with fibromyalgia, by looking at single nucleotide polymorphisms in 34 fibromyalgia candidate-genes, at the interactions between genes, and at the gene-physical activity interactions. We extracted DNA from saliva of 276 fibromyalgia women to analyze gene-polymorphisms. Accelerometers registered physical activity and sedentary behavior. Fatigue was assessed with the Multidimensional Fatigue Inventory. Based on the Bonferroni's and False Discovery Rate values, we found that the genotype of the rs4453709 polymorphism (sodium channel protein type 9 subunit alpha, SCN9A, gene) was related to reduced motivation (AT carriers showed the highest reduced motivation) and reduced activity (AA carriers showed the lowest reduced activity). Carriers of the heterozygous genotype of the rs1801133 (methylene tetrahydrofolate reductase, MTHFR, gene) or rs4597545 (SCN9A gene) polymorphisms who were physically active reported lower scores on fatigue compared to their inactive counterparts. Highly sedentary carriers of the homozygous genotype of the rs7607967 polymorphism (AA/GG genotype; SCN9A gene) presented more reduced activity (a dimension of fatigue) than those with lower levels of sedentary behavior. Collectively, findings from the present study suggest that the contribution of genetics and gene-physical activity interaction to fatigue in fibromyalgia is modest.

Keywords: accelerometry; chronic pain; epidemiology; gene polymorphism; rehabilitation; treatment.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Individual associations of the genotype of the rs4453709 polymorphism (SCN9A gene) with dimensions of fatigue; i.e., reduced motivation (left panel) and reduced activity (right panel). Note. SCN9A, sodium voltage-gated channel alpha subunit 9 gene; MFI, multidimensional fatigue inventory (MFI, scores range 0–20). According to the p- and false discovery rate (FDR) values, all these associations of genotype and fatigue were significant.
Figure 2
Figure 2
Associations of the interaction of the MTHFR gene (rs1801133 polymorphism)-physical activity with dimensions of fatigue; physical fatigue (left panel) and reduced motivation (right panel). Note. MTHFR, methylene tetrahydrofosfate reductase gene; MVPA, moderate to vigorous physical activity; MFI, multidimensional fatigue inventory (scores range 0–20). Physical activity was objectively measured using triaxial accelerometers GT3X+ (Actigraph, Pensacola, FL, USA). We dichotomized data of physical activity according to the fulfilment (yes vs. no) of the physical activity recommendations (≥150 min/week) of MVPA in bouts of, at least, 10 min of length. According to the p- and false discovery rate (FDR) values, all these gene-physical activity interactions were significant.
Figure 3
Figure 3
Associations of the interaction of the SCN9A gene (rs4597545 polymorphism)-physical activity with mental fatigue (a dimension of fatigue). Note. SCN9A, sodium voltage-gated channel alpha subunit 9 gene; MVPA, moderate to vigorous physical activity; MFI, multidimensional fatigue inventory (scores range 0–20). Physical activity was objectively measured using triaxial accelerometers GT3X+ (Actigraph, Pensacola, FL, USA). We dichotomized data of physical activity according to the fulfilment (yes vs. no) of the physical activity recommendations (≥150 min/week of MVPA in bouts of, at least, 10 min of length. According to the p- and false discovery rate (FDR) values, all these gene-physical activity interactions were significant.
Figure 4
Figure 4
Associations of the interaction of the SCN9A gene (rs7607967 polymorphisms)-sedentary behavior with reduced activity (a dimension of fatigue). Note. SCN9A, sodium voltage-gated channel alpha subunit 9 gene; MFI, multidimensional fatigue inventory (scores range 0–20). Sedentary behavior as objectively measured using triaxial accelerometers GT3X+ (Actigraph, Pensacola, FL, USA). We dichotomized data of sedentary behavior (low vs. high) using the mean as the cut-off value. According to the p and false discovery rate (FDR) values, this gene-sedentary behavior interaction was significant.
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