THU0468 THE INTERACTIONS OF PHYSICAL ACTIVITY LEVELS WITH THE SODIUM CHANNEL PROTEIN TYPE 9 SUBUNIT ALPHA AND METHYLENE TETRAHYDROFOLATE REDUCTASE GENES ARE ASSOCIATED WITH FATIGUE IN WOMEN WITH FIBROMYALGIA
Authors: Fernando Estevez-Lopez, Diego Salazar-Tortosa, Blanca Gavilán Carrera, Virginia A Aparicio, Pedro Acosta-Manzano, Víctor Segura-Jiménez, Inmaculada C Alvarez-Gallardo, Ana Carbonell-Baeza, Diego Munguía-Izquierdo, Rinie Geenen, Eliana Lacerda, Manuel Delgado-Fernández, Luis J Martínez-González, Jonatan R Ruiz, María J Álvarez-Cubero
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> People with fibromyalgia identify fatigue as one of the main symptoms of the disease [1]. It is hypothesised that the pathogenesis of fibromyalgia involves a genetic susceptibility that is modulated by environmental factors [2] <h3>Objectives</h3> To examine the possible role of genetic susceptibility for fatigue in southern Spanish women with fibromyalgia, by looking at the possible associations of fatigue and single nucleotide polymorphisms in 34 fibromyalgia candidate-genes, at the interactions between genes, and at the associations between gene-physical activity. <h3>Methods</h3> In this cross-sectional study participated 276 women with fibromyalgia. We extracted DNA from saliva in order to analyse gene-polymorphisms related to fibromyalgia susceptibility, symptoms, or potential mechanisms. Accelerometers registered the participants' physical activity and sedentary time. Five dimensions of fatigue were assessed with the Multidimensional Fatigue Inventory. Age, body fat (%), and analgesics and antidepressants consumption were considered as confounders in all analyses. Based on the Bonferroni's and False Discovery Rate (FDR) values, the statistical significance was interpreted. <h3>Results</h3> AT carriers of the rs4453709 polymorphism (sodium channel protein type 9 subunit alpha, SCN9A, gene) showed the highest scores on fatigue. Carriers of the heterozygous genotype of the rs1801133 (methylene tetrahydrofolate reductase, MTHFR, gene) or rs4597545 (SCN9A gene) polymorphisms who were physically active reported lower fatigue compared to their inactive counterparts. Highly sedentary carriers of the homozygous genotype of the rs7607967 polymorphism (AA/GG genotype; SCN9A gene) presented higher fatigue than those with lower levels of sedentary time. <h3>Conclusion</h3> Physical (in)activity behaviours and the SCN9A and MTHFR genes were jointly related to fatigue. Thereby, the potential benefits of following an active lifestyle might be observed more clearly in women with fibromyalgia genetically predispose to higher levels of fatigue. <h3>References</h3> [1] Bennett RM, et al. BMC Musculoskelet Disord 2010;11:134. doi:10.1186/1471-2474-11-134 [2] McBeth J, Mulvey MR. Nat Rev Rheumatol 2012;8:108–16. doi:10.1038/nrrheum.2011.216 <h3>Acknowledgement</h3> This work was supported by the Spanish Ministry of Economy and Competitiveness [I+D+i DEP2010-15639, I+D+i DEP2013-40908-R to M.D.-F.; BES-2014-067612 to F.E.-L.]; the Spanish Ministry of Education [FPU13/03410 to D.S.-T.; FPU 15/00002 to B.G.C]; the Consejería de Turismo, Comercio y Deporte, Junta de Andalucía [CTCD-201000019242-TRA to MD-F]; and the University of Granada, Plan Propio de Investigación 2016, Excellence actions: Units of Excellence; Unit of Excellence on Exercise and Health (UCEES). <h3>Disclosure of Interests</h3> None declared