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

Fernando Estevez-López; Juan M. Guerrero-González; Diego Salazar-Tortosa; Daniel Camiletti-Moirón; Blanca Gavilán-Carrera; Virginia A. Aparicio; Pedro Acosta-Manzano; Inmaculada C. Álvarez-Gallardo; Víctor Segura-Jimenez; Alberto Soriano-Maldonado; Rinie Geenen; Manuel Delgado-Fernández; Luis J. Martínez-González; Jonatan R. Ruiz; María J. Álvarez-Cubero

doi:10.1093/rheumatology/keab911

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

Fernando Estevez-López, Juan M. Guerrero-González^*, Diego Salazar-Tortosa, Daniel Camiletti-Moirón, Blanca Gavilán-Carrera, Virginia A. Aparicio, Pedro Acosta-Manzano, Inmaculada C. Álvarez-Gallardo, Víctor Segura-Jimenez, Alberto Soriano-Maldonado, Rinie Geenen, Manuel Delgado-Fernández, Luis J. Martínez-González, Jonatan R. Ruiz, María J. Álvarez-Cubero

^*Corresponding author for this work

Child and Adolescent Psychiatry / Psychology

Research output: Contribution to journal › Article › Academic › peer-review

8 Citations (Scopus)

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 FM.

Methods:
Saliva samples from 274 women with FM [mean (s.d.) age 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 (5-hydroxytryptamine receptor 2A, HTR2A) were individually related to algometer scores. The interaction of rs4818 (catechol-O-methyltransferase, COMT) and rs1799971 (opioid receptor μ gene, OPRM1) was related to pain catastrophizing. Five gene-behaviour interactions were significant: The interactions of sedentary behaviour with rs1383914 (adrenoceptor alpha 1A, ADRA1A), rs6860 (charged multivesicular body protein 1A, CHMP1A), rs4680 (COMT), rs165599 (COMT) and rs12994338 (SCN9A) on bodily pain subscale of the Short Form 36. Furthermore, the meta-Analysis showed an association between rs4680 (COMT) and severity of FM 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 FM. Future research should examine whether reducing sedentary behaviour is particularly beneficial for reducing pain in women with genetic susceptibility to pain.

Original language	English
Pages (from-to)	3180-3191
Number of pages	12
Journal	Rheumatology (United Kingdom)
Volume	61
Issue number	8
DOIs	https://doi.org/10.1093/rheumatology/keab911
Publication status	Published - 3 Aug 2022

Bibliographical note

Publisher Copyright:
© 2021 The Author(s). Published by Oxford University Press on behalf of the British Society for Rheumatology.

Funding:
This work was supported by the Spanish Ministry of Economy and Competitiveness (IþDþi DEP2010-15639, IþDþi 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.; FPU15/0002 to B.G.-C.), the Consejerıa de Turismo, Comercio y
Deporte, Junta de Andalucıa (CTCD-201000019242-TRA to M.D.-F.), the Consejerıa de Salud, Junta de Andalucıa (PI-0520-2016 to M.D.-F.) and the University of Granada, Plan Propio de Investigacio´ n 2016, Excellence
actions: Units of Excellence; Unit of Excellence on Exercise and Health (UCEES). The funders of the present study did not have any role in the study design,
data collection and analyses, decision to publish or preparation of the manuscript.

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Cite this

Estevez-López, F., Guerrero-González, J. M., Salazar-Tortosa, D., Camiletti-Moirón, D., Gavilán-Carrera, B., Aparicio, V. A., Acosta-Manzano, P., Álvarez-Gallardo, I. C., Segura-Jimenez, V., Soriano-Maldonado, A., Geenen, R., Delgado-Fernández, M., Martínez-González, L. J., Ruiz, J. R., & Álvarez-Cubero, M. J. (2022). Interplay between genetics and lifestyle on pain susceptibility in women with fibromyalgia: The al-Ándalus project. Rheumatology (United Kingdom), 61(8), 3180-3191. https://doi.org/10.1093/rheumatology/keab911

@article{f381d8ca9003455681ab99cb3c019efb,

title = "Interplay between genetics and lifestyle on pain susceptibility in women with fibromyalgia: The al-{\'A}ndalus 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 FM. Methods: Saliva samples from 274 women with FM [mean (s.d.) age 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 (5-hydroxytryptamine receptor 2A, HTR2A) were individually related to algometer scores. The interaction of rs4818 (catechol-O-methyltransferase, COMT) and rs1799971 (opioid receptor μ gene, OPRM1) was related to pain catastrophizing. Five gene-behaviour interactions were significant: The interactions of sedentary behaviour with rs1383914 (adrenoceptor alpha 1A, ADRA1A), rs6860 (charged multivesicular body protein 1A, CHMP1A), rs4680 (COMT), rs165599 (COMT) and rs12994338 (SCN9A) on bodily pain subscale of the Short Form 36. Furthermore, the meta-Analysis showed an association between rs4680 (COMT) and severity of FM 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 FM. Future research should examine whether reducing sedentary behaviour is particularly beneficial for reducing pain in women with genetic susceptibility to pain.",

author = "Fernando Estevez-L{\'o}pez and Guerrero-Gonz{\'a}lez, {Juan M.} and Diego Salazar-Tortosa and Daniel Camiletti-Moir{\'o}n and Blanca Gavil{\'a}n-Carrera and Aparicio, {Virginia A.} and Pedro Acosta-Manzano and {\'A}lvarez-Gallardo, {Inmaculada C.} and V{\'i}ctor Segura-Jimenez and Alberto Soriano-Maldonado and Rinie Geenen and Manuel Delgado-Fern{\'a}ndez and Mart{\'i}nez-Gonz{\'a}lez, {Luis J.} and Ruiz, {Jonatan R.} and {\'A}lvarez-Cubero, {Mar{\'i}a J.}",

note = "Publisher Copyright: {\textcopyright} 2021 The Author(s). Published by Oxford University Press on behalf of the British Society for Rheumatology. Funding: This work was supported by the Spanish Ministry of Economy and Competitiveness (I{\th}D{\th}i DEP2010-15639, I{\th}D{\th}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.; FPU15/0002 to B.G.-C.), the Consejerıa de Turismo, Comercio y Deporte, Junta de Andalucıa (CTCD-201000019242-TRA to M.D.-F.), the Consejerıa de Salud, Junta de Andalucıa (PI-0520-2016 to M.D.-F.) and the University of Granada, Plan Propio de Investigacio´ n 2016, Excellence actions: Units of Excellence; Unit of Excellence on Exercise and Health (UCEES). The funders of the present study did not have any role in the study design, data collection and analyses, decision to publish or preparation of the manuscript.",

year = "2022",

month = aug,

day = "3",

doi = "10.1093/rheumatology/keab911",

language = "English",

volume = "61",

pages = "3180--3191",

journal = "Rheumatology (United Kingdom)",

issn = "1462-0324",

publisher = "Oxford University Press",

number = "8",

}

Estevez-López, F, Guerrero-González, JM, Salazar-Tortosa, D, Camiletti-Moirón, D, Gavilán-Carrera, B, Aparicio, VA, Acosta-Manzano, P, Álvarez-Gallardo, IC, Segura-Jimenez, V, Soriano-Maldonado, A, Geenen, R, Delgado-Fernández, M, Martínez-González, LJ, Ruiz, JR & Álvarez-Cubero, MJ 2022, 'Interplay between genetics and lifestyle on pain susceptibility in women with fibromyalgia: The al-Ándalus project', Rheumatology (United Kingdom), vol. 61, no. 8, pp. 3180-3191. https://doi.org/10.1093/rheumatology/keab911

TY - JOUR

T1 - Interplay between genetics and lifestyle on pain susceptibility in women with fibromyalgia

T2 - The al-Ándalus project

AU - Estevez-López, Fernando

AU - Guerrero-González, Juan M.

AU - Salazar-Tortosa, Diego

AU - Camiletti-Moirón, Daniel

AU - Gavilán-Carrera, Blanca

AU - Aparicio, Virginia A.

AU - Acosta-Manzano, Pedro

AU - Álvarez-Gallardo, Inmaculada C.

AU - Segura-Jimenez, Víctor

AU - Soriano-Maldonado, Alberto

AU - Geenen, Rinie

AU - Delgado-Fernández, Manuel

AU - Martínez-González, Luis J.

AU - Ruiz, Jonatan R.

AU - Álvarez-Cubero, María J.

N1 - Publisher Copyright: © 2021 The Author(s). Published by Oxford University Press on behalf of the British Society for Rheumatology. Funding: This work was supported by the Spanish Ministry of Economy and Competitiveness (IþDþi DEP2010-15639, IþDþi 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.; FPU15/0002 to B.G.-C.), the Consejerıa de Turismo, Comercio y Deporte, Junta de Andalucıa (CTCD-201000019242-TRA to M.D.-F.), the Consejerıa de Salud, Junta de Andalucıa (PI-0520-2016 to M.D.-F.) and the University of Granada, Plan Propio de Investigacio´ n 2016, Excellence actions: Units of Excellence; Unit of Excellence on Exercise and Health (UCEES). The funders of the present study did not have any role in the study design, data collection and analyses, decision to publish or preparation of the manuscript.

PY - 2022/8/3

Y1 - 2022/8/3

N2 - 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 FM. Methods: Saliva samples from 274 women with FM [mean (s.d.) age 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 (5-hydroxytryptamine receptor 2A, HTR2A) were individually related to algometer scores. The interaction of rs4818 (catechol-O-methyltransferase, COMT) and rs1799971 (opioid receptor μ gene, OPRM1) was related to pain catastrophizing. Five gene-behaviour interactions were significant: The interactions of sedentary behaviour with rs1383914 (adrenoceptor alpha 1A, ADRA1A), rs6860 (charged multivesicular body protein 1A, CHMP1A), rs4680 (COMT), rs165599 (COMT) and rs12994338 (SCN9A) on bodily pain subscale of the Short Form 36. Furthermore, the meta-Analysis showed an association between rs4680 (COMT) and severity of FM 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 FM. Future research should examine whether reducing sedentary behaviour is particularly beneficial for reducing pain in women with genetic susceptibility to pain.

AB - 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 FM. Methods: Saliva samples from 274 women with FM [mean (s.d.) age 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 (5-hydroxytryptamine receptor 2A, HTR2A) were individually related to algometer scores. The interaction of rs4818 (catechol-O-methyltransferase, COMT) and rs1799971 (opioid receptor μ gene, OPRM1) was related to pain catastrophizing. Five gene-behaviour interactions were significant: The interactions of sedentary behaviour with rs1383914 (adrenoceptor alpha 1A, ADRA1A), rs6860 (charged multivesicular body protein 1A, CHMP1A), rs4680 (COMT), rs165599 (COMT) and rs12994338 (SCN9A) on bodily pain subscale of the Short Form 36. Furthermore, the meta-Analysis showed an association between rs4680 (COMT) and severity of FM 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 FM. Future research should examine whether reducing sedentary behaviour is particularly beneficial for reducing pain in women with genetic susceptibility to pain.

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U2 - 10.1093/rheumatology/keab911

DO - 10.1093/rheumatology/keab911

M3 - Article

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AN - SCOPUS:85159938851

SN - 1462-0324

VL - 61

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JO - Rheumatology (United Kingdom)

JF - Rheumatology (United Kingdom)

IS - 8

ER -

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

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