Gene-physical activity interaction with pain, fatigue, and resilience in women with fibromyalgia

Summary People with fibromyalgia often experience chronic pain and other non-painful (e.g., fatigue symptoms). This disease has not cure yet. Thus, adaptation to the disease is strived for. In the dynamic process of adaptation, people’s strengths play a crucial role. Family aggregation suggests, but does not conclude, genetic susceptibility to fibromyalgia. In fibromyalgia, lifestyle (e.g., physical activity) is a powerful marker of health. However, previous research did not consider the interplay of genetic and behavioural factors. This knowledge could be the basement for providing a more personalised care. The overall aim of the present Doctoral Thesis was to enhance the understanding of the genetics of fibromyalgia, paying attention to the potential gene-gene and gene-lifestyle (i.e., time spent on physical activity and sedentary behaviour) interactions, and their association with pain, fatigue, and resilience. To do so, 64 polymorphisms of 34 fibromyalgia candidate-genes were studied in a well-characterised sample of southern Spanish women. The findings of the present Doctoral Thesis informed that susceptibility to fibromyalgia and its core symptoms (i.e., pain and fatigue) may have a genetic component, which is mostly related to dysfunctions in neurotransmission. Moreover, the sodium voltage-gated channel alpha subunit 9 (SCN9A) gene was the one that showed the most robust associations with the phenotype of fibromyalgia. The SCN9A gene encodes the Na(v)1.7 sodium channel, which suggests that blocking the gain-of-function of this type of channel may lead to beneficial effects on living with fibromyalgia. Furthermore, an active lifestyle may help to modulate an unfavourable genetic predisposition to pain, fatigue, and resilience. The associations of physical activity behaviours with a favourable phenotype might be more clearly observable for some genotypes of women with fibromyalgia. Resumen La fibromialgia, enfermedad caracterizada por dolor cronico y fatiga, no tiene cura todavia. Por ello, es deseable conseguir adaptarse a la enfermedad. Dado que hay agregacion familiar en la fibromialgia, se ha sugerido que hay susceptibilidad genetica a esta enfermedad. El estilo de vida de las personas con fibromialgia (por ejemplo, la actividad fisica) es un importante marcador de salud. Sin embargo, la interaccion entre factores geneticos y comportamentales aun no ha sido estudiada. Este conocimiento podria suponer los cimientos para ofrecer un cuidado mas individualizado. El objetivo general de esta Tesis Doctoral ha sido mejorar el conocimiento de la genetica de la fibromialgia, prestando espacial atencion a las interacciones gen-gen y gen-factores ambientales (i.e., actividad fisica y comportamiento sedentario). Para ello, se analizaron 64 polimorfismos de 34 genes candidatos en una muestra bien definida de mujeres Andaluzas (sur de Espana). Los hallazgos de la presente Tesis Doctoral indican que la susceptibilidad a la fibromialgia y sus sintomas cardinales (como el dolor, la fatiga y la baja resiliencia) pueden tener un componente genetico que, sobre todo, esta relacionado con alteraciones en la neurotransmision. El gen SCN9A fue el que se asocio de forma mas robusta con el fenotipo de la fibromialgia. Este gen codifica un el canal de sodio Na(v)1.7, lo que sugiere que bloqueando este tipo de canal podria ser beneficioso en las personas con fibromialgia. Ademas, un estilo de vida activo puede modular una predisposicion genetica a tener niveles altos de dolor y fatiga, asi como bajos de resiliencia. La actividad fisica podria ser particularmente favorable para algunas mujeres con fibromialgia dependiendo de su genotipo.