Interplay between genetics and lifestyle on pain susceptibility in women with fibromyalgia: the al-Ándalus project

Abstract

Objectives It is widely acknowledged that the experience of pain is promoted by both genetic susceptibility and environmental factors such as engaging in physical activity (PA) and that pain-related cognitions are also important. Thus, the purpose of the present study was to test the association of 64 polymorphisms (34 candidate-genes) and the gene-gene, gene-PA, and gene-sedentary behaviour interactions with pain and pain-related cognitions in women with fibromyalgia. Methods Saliva samples from 274 women with fibromyalgia (aged 51.7 ± 7.7 years) were collected for extracting DNA. We measured PA and sedentary behaviour by accelerometers for a week, pain with algometry and questionnaires, and pain-related cognitions with questionnaires. To assess the robustness of the results, a meta-analysis was also performed. Results The rs6311 and rs6313 polymorphisms (HTR2A) were individually related to algometer scores. The interaction of rs4818 (COMT) and rs1799971 (OPRM1) was related to pain catastrophizing. Five gene-behaviour interactions were significant: the interactions of sedentary behaviour with rs1383914 (ADR1A), rs6860 (CHMP1A), rs4680 (COMT), rs165599 (COMT) and rs12994338 (SCN9A) on bodily pain subscale of the SF-36. Furthermore, the meta-analysis showed an association between rs4680 (COMT) and severity of fibromyalgia symptoms (codominant model, p-value: 0.032). Conclusion The HTR2A gene (individually), COMT and OPRM1 gene-gene interaction, and the interactions of sedentary behaviour with ADRA1A, CHMP1A, COMT, and SCN9A genes were associated with pain-related outcomes. Collectively, findings from the present study indicate a modest contribution of genetics and gene-sedentary behaviour interaction to pain and pain catastrophizing in women with fibromyalgia. Future research should examine whether reducing sedentary behaviour is particularly beneficial for reducing pain in women with genetic susceptibility to pain.

Association of polymorphism of the enzyme catechol-o-methyltransferase with fibromialgic syndrome and its clinical repercussions

“…In another study, which evaluated 274 women with FMS, a statistically signi cant association was observed between physical inactivity and symptom severity with the rs4680 SNP. Regarding lifestyle, more than 75% of the sample of our study is in the overweight or obese range, and almost 90% do not perform any type of physical activity (42).…”

A Comprehensive Review of the Genetic and Epigenetic Contributions to the Development of Fibromyalgia

“…A possible explanation is that rs4680 may be overrepresented within the FM population. Since rs4680 is associated with increased pain symptoms [ 12 , 32 , 33 , 36 , 41 ], it is not surprising that individuals with rs4680 report an increased severity of FM-associated symptoms.…”

“…Similar to rs4680, rs4818 is associated with pain sensitivity [ 32 , 38 ]. The presence of both rs4818 and a SNP (rs1799971) in the opioid receptor mu 1 ( OPRM1 ) gene is associated with pain catastrophizing [ 41 ]. Additional variants have been evaluated, with some showing an association with FM development.…”

Fatores genéticos associados à fibromialgia: uma revisão narrativa

“…Por isso, polimorfismos em genes relacionados a neurotransmissores e outros componentes que participam dessa via, agindo na modulação da dor como serotonina, norepinefrina, dopamina, entre outros, são frequentemente encontrados em estudos de associação genética com a FM (Lee et al, 2012;Ablin & Buskila, 2014;Zorina-Lichtenwalter et al, 2016). Porém, outros genes-alvo têm surgido, relacionados às vias responsáveis pelos mecanismos dos mais diversos sintomas que podem acometer esses pacientes, como inflamação, vascularização, estresse oxidativo, ciclo celular, entre outros (Karakus et al, 2012;Yigit et al, 2013;Inanir et al, 2015;da Silveira Alves et al, 2020;Estévez-López et al, 2021b).…”

“…CHMP1A pertence à família da proteína modificadora da cromatina e são fundamentais para a formação de corpos multivesiculares endocíticos (MVBs) e na regulação da progressão do ciclo celular (Tsang et al, 2006). O genótipo TT e o alelo T do CHMP1A rs6860 foram associados a uma suscetibilidade à fibromialgia em mulheres do sul da Espanha (Estévez-López et al, 2018a) e recentemente esse polimorfismo foi associado a um aumento do comportamento sedentário, uma sub-escala na avaliação de dor corporal, em mulheres com FM (Estévez-López et al, 2021b).…”